{"entity": "journal", "iuid": "513ed539c03245c6bf86605e8e7477b3", "timestamp": "2026-07-14T00:37:06.869Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Transl%20Psychiatry.json"}, "display": {"href": "https://publications.scilifelab.se/journal/Transl%20Psychiatry"}}, "title": "Transl Psychiatry", "issn": "2158-3188", "issn-l": "2158-3188", "publications_count": 22, "publications": [{"entity": "publication", "iuid": "b541a4128e1345e8bf9d8db8209ae7a3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b541a4128e1345e8bf9d8db8209ae7a3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b541a4128e1345e8bf9d8db8209ae7a3"}}, "title": "Transcription of GABAA receptor subunits in circulating monocytes and association to emotional brain function in premenstrual dysphoric disorder.", "authors": [{"family": "Stiernman", "given": "Louise", "initials": "L", "orcid": "0000-0002-9662-981X", "researcher": {"href": "https://publications.scilifelab.se/researcher/168bd84159814cd88be040d84a4c57a7.json"}}, {"family": "Comasco", "given": "Erika", "initials": "E"}, {"family": "Johansson", "given": "Maja", "initials": "M"}, {"family": "Bixo", "given": "Marie", "initials": "M", "orcid": "0000-0002-4988-1967", "researcher": {"href": "https://publications.scilifelab.se/researcher/defb095eecec4c33b25851f9553fc320.json"}}], "type": "journal article", "published": "2025-07-23", "journal": {"title": "Transl Psychiatry", "issn": "2158-3188", "volume": "15", "issue": "1", "pages": "255", "issn-l": "2158-3188"}, "abstract": "Premenstrual dysphoric disorder (PMDD) has been hypothesized to be related to an altered sensitivity of the \u03b3-aminobutyric acid type A (GABAA) receptor to progesterone-derived neurosteroids. GABAA receptor sensitivity to neurosteroid-modulation is dependent on its subunit composition. In the present study, we used quantitative reverse transcription polymerase chain reactions (RT-qPCR) to compare messenger ribonucleic acid (mRNA) expression of GABAA receptor subunits in peripheral mononuclear cells (PBMCs) across the menstrual cycle in 29 women with PMDD and 27 controls. We related mRNA subunit expression to serum levels of neurosteroids and to functional activation of the amygdala, a key brain region involved in emotion generation, measured using functional magnetic resonance imaging (fMRI). Women with PMDD had lower mRNA expression of the delta GABAA receptor subunit during the symptomatic, luteal phase (compared to the asymptomatic, follicular phase) of the menstrual cycle. Lower delta mRNA expression was related to higher amygdala activation in PMDD women. GABAA receptors incorporating the delta subunit are especially sensitive to neurosteroid modulation. It is possible that the mood symptoms of PMDD are mediated by an inability to effectively adjust the expression of this receptor type in response to neurosteroid fluctuations, leading to dysregulation GABAergic tone and increased activity in emotion-generating brain circuits.", "doi": "10.1038/s41398-025-03465-6", "pmid": "40701967", "labels": {"Clinical Genomics": "Service", "Clinical Genomics Ume\u00e5": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12287299"}, {"db": "pii", "key": "10.1038/s41398-025-03465-6"}], "notes": [], "created": "2025-11-26T09:17:53.937Z", "modified": "2025-11-26T09:17:54.289Z"}, {"entity": "publication", "iuid": "e0d705c2a3ee47979f31a000531e4fd6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e0d705c2a3ee47979f31a000531e4fd6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e0d705c2a3ee47979f31a000531e4fd6"}}, "title": "Heritability and polygenic load for comorbid anxiety and depression.", "authors": [{"family": "Tabrizi", "given": "Fara", "initials": "F", "orcid": "0000-0003-4009-0090", "researcher": {"href": "https://publications.scilifelab.se/researcher/ee28a29d54c344eebcb95a56e6707b8a.json"}}, {"family": "Ros\u00e9n", "given": "J\u00f6rgen", "initials": "J"}, {"family": "Gr\u00f6nvall", "given": "Hampus", "initials": "H"}, {"family": "William-Olsson", "given": "Victor Rahimzadeh", "initials": "VR"}, {"family": "Arner", "given": "Erik", "initials": "E"}, {"family": "Magnusson", "given": "Patrik Ke", "initials": "PK", "orcid": "0000-0002-7315-7899", "researcher": {"href": "https://publications.scilifelab.se/researcher/b277b6387de142bbab91fad82d9eff09.json"}}, {"family": "Palm", "given": "Camilla", "initials": "C"}, {"family": "Larsson", "given": "Henrik", "initials": "H", "orcid": "0000-0002-6851-3297", "researcher": {"href": "https://publications.scilifelab.se/researcher/21f2cca2f6b74c5393c0fc33bcf15ee6.json"}}, {"family": "Viktorin", "given": "Alexander", "initials": "A", "orcid": "0000-0003-2141-2816", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f02b9aad56348c28f639bf231748096.json"}}, {"family": "Bernhardsson", "given": "Jens", "initials": "J"}, {"family": "Bj\u00f6rkdahl", "given": "Johanna", "initials": "J"}, {"family": "Jansson", "given": "Billy", "initials": "B"}, {"family": "Sundin", "given": "\u00d6rjan", "initials": "\u00d6"}, {"family": "Zhou", "given": "Xuan", "initials": "X"}, {"family": "Speed", "given": "Doug", "initials": "D", "orcid": "0000-0002-0096-9765", "researcher": {"href": "https://publications.scilifelab.se/researcher/5144d83e395d43319b86e1af1e0b398b.json"}}, {"family": "\u00c5hs", "given": "Fredrik", "initials": "F"}], "type": "journal article", "published": "2025-03-27", "journal": {"title": "Transl Psychiatry", "issn": "2158-3188", "volume": "15", "issue": "1", "pages": "98", "issn-l": "2158-3188"}, "abstract": "Anxiety and depression commonly occur together resulting in worse health outcomes than when they occur in isolation. We aimed to determine whether the genetic liability for comorbid anxiety and depression was greater than when anxiety or depression occurred alone. Data from 12,792 genotyped twins (ages 38-85) were analysed, including 1,986 complete monozygotic and 1,594 complete dizygotic pairs. Outcomes were prescription of antidepressant and anxiolytic drugs, as defined by the World Health Organization Anatomical Therapeutic Chemical Classification System (ATC) convention, for comorbid anxiety and depression (n = 1028), anxiety only (n = 718), and depression only (n = 484). Heritability of each outcome was estimated using twin modelling, and the influence of common genetic variation was assessed from polygenic scores (PGS) for depressive symptoms, anxiety, and 40 other traits. Heritability of comorbid anxiety and depression was 79% compared with 41% for anxiety and 50% for depression alone. The PGS for depressive symptoms likewise predicted more variation in comorbid anxiety and depression (adjusted odds ratio per SD PGS = 1.53, 95% CI = 1.43-1.63; \u0394R2 = 0.031, \u0394AUC = 0.044) than the other outcomes, with nearly identical results when comorbid anxiety and depression was defined by International Classification of Diseases (ICD) diagnoses (adjusted odds ratio per SD PGS = 1.70, 95% CI = 1.53-1.90; \u0394R2 = 0.036, \u0394AUC = 0.051). Individuals in the highest decile of PGS for depressive symptoms had over 5 times higher odds of being prescribed medication for comorbid anxiety and depression compared to those in the lowest decile. While results on a predominant role of depressive symptoms may have been biased by the size and heterogeneity of available data bases, they are consistent with the conclusion that genetic factors explain substantially more variation in comorbid anxiety and depression than anxiety or depression alone.", "doi": "10.1038/s41398-025-03325-3", "pmid": "40140358", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11947153"}, {"db": "pii", "key": "10.1038/s41398-025-03325-3"}], "notes": [], "created": "2025-11-28T10:44:51.862Z", "modified": "2025-11-28T10:44:52.088Z"}, {"entity": "publication", "iuid": "917f69c53a0c42acb20c8b50676c0cde", "links": {"self": {"href": "https://publications.scilifelab.se/publication/917f69c53a0c42acb20c8b50676c0cde.json"}, "display": {"href": "https://publications.scilifelab.se/publication/917f69c53a0c42acb20c8b50676c0cde"}}, "title": "Irradiation and lithium treatment alter the global DNA methylation pattern and gene expression underlying a shift from gliogenesis towards neurogenesis in human neural progenitors.", "authors": [{"family": "Neofytou", "given": "Christina", "initials": "C", "orcid": "0000-0002-1547-7085", "researcher": {"href": "https://publications.scilifelab.se/researcher/757792036d8040e8bebe763443aab360.json"}}, {"family": "Backlund", "given": "Alexandra", "initials": "A"}, {"family": "Blomgren", "given": "Klas", "initials": "K", "orcid": "0000-0002-0476-7271", "researcher": {"href": "https://publications.scilifelab.se/researcher/2fb3b554177d481ebc9d4aa0f3b1fbc4.json"}}, {"family": "Hermanson", "given": "Ola", "initials": "O", "orcid": "0000-0001-9320-7921", "researcher": {"href": "https://publications.scilifelab.se/researcher/127407b365334524be30de6c31aec5ba.json"}}], "type": "journal article", "published": "2023-07-13", "journal": {"title": "Transl Psychiatry", "issn": "2158-3188", "volume": "13", "issue": "1", "pages": "258", "issn-l": "2158-3188"}, "abstract": "Central nervous system (CNS) tumors account for almost a third of pediatric cancers and are the largest contributor to cancer-related death in children. Cranial radiation therapy (CRT) is, often in combination with chemotherapy and surgery, effective in the treatment of high-grade childhood brain cancers, but it has been associated with late complications in 50-90% of survivors, such as decline in cognition and mood, decreased social competence, and fatigue. A leading hypothesis to explain the decline in cognition, at least partially, is injury to the neural stem and progenitor cells (NSPCs), which leads to apoptosis and altered fate choice, favoring gliogenesis over neurogenesis. Hence, treatments harnessing neurogenesis are of great relevance in this context. Lithium, a well-known mood stabilizer, has neuroprotective and antitumor effects and has been found to reverse irradiation-induced damage in rodents, at least in part by regulating the expression of the glutamate decarboxylase 2 gene (Gad2) via promoter demethylation in rat NSPCs. Additionally, lithium was shown to rescue irradiation-induced cognitive defects in mice. Here, we show that irradiation (IR) alone or in combination with lithium chloride (LiCl) caused major changes in gene expression and global DNA methylation in iPSC-derived human NSPCs (hNSPCs) compared to untreated cells, as well as LiCl-only-treated cells. The pattern of DNA methylation changes after IR-treatment alone was stochastic and observed across many different gene groups, whereas differences in DNA methylation after LiCl-treatment of irradiated cells were more directed to specific promoters of genes, including genes associated with neurogenesis, for example GAD2. Interestingly, IR and IR + LiCl treatment affected the promoter methylation and expression of several genes encoding factors involved in BMP signaling, including the BMP antagonist gremlin1. We propose that lithium in addition to promoting neuronal differentiation, also represses glial differentiation in hNSPCs with DNA methylation regulation being a key mechanism of action.", "doi": "10.1038/s41398-023-02560-w", "pmid": "37443041", "labels": {"NGI Short read": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10345108"}, {"db": "pii", "key": "10.1038/s41398-023-02560-w"}], "notes": [], "created": "2023-10-11T10:47:25.231Z", "modified": "2023-10-19T12:53:20.882Z"}, {"entity": "publication", "iuid": "eec4c83790864c44b1c29201e9e0559a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/eec4c83790864c44b1c29201e9e0559a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/eec4c83790864c44b1c29201e9e0559a"}}, "title": "Accelerated epigenetic aging in women with emotionally unstable personality disorder and a history of suicide attempts.", "authors": [{"family": "Bostr\u00f6m", "given": "Adrian Desai E", "initials": "ADE", "orcid": "0000-0001-8604-9638", "researcher": {"href": "https://publications.scilifelab.se/researcher/5ace74b9a4894d82a16e7ff445bbcea6.json"}}, {"family": "Andersson", "given": "Peter", "initials": "P"}, {"family": "Jamshidi", "given": "Esmail", "initials": "E"}, {"family": "Wilczek", "given": "Alexander", "initials": "A"}, {"family": "Nilsonne", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Rask-Andersen", "given": "Mathias", "initials": "M"}, {"family": "\u00c5sberg", "given": "Marie", "initials": "M"}, {"family": "Jokinen", "given": "Jussi", "initials": "J"}], "type": "journal article", "published": "2023-02-22", "journal": {"title": "Transl Psychiatry", "issn": "2158-3188", "volume": "13", "issue": "1", "pages": "66", "issn-l": "2158-3188"}, "abstract": "Emotional unstable personality disorder (EUPD; previously borderline personality disorder, BPD) is associated with excess natural-cause mortality, comorbid medical conditions, poor health habits and stress related epigenomic alterations. Previous studies demonstrated that GrimAge - a state-of-the-art epigenetic age (EA) estimator - strongly predicts mortality risk and physiological dysregulation. Herein, we utilize the GrimAge algorithm to investigate whether women with EUPD and a history of recent suicide attempts exhibit EA acceleration (EAA) in comparison to healthy controls. Genome-wide methylation patterns were measured using the Illumina Infinum Methylation Epic BeadChip in whole blood from 97 EUPD patients and 32 healthy controls. The control group was significantly older (p < 0.0001) and reported lesser exposure to violent behavior in both youth and adulthood (p < 0.0001). Groups were otherwise comparable regarding gender, BMI, or tobacco usage (p > 0.05). EA estimator DNAmGrimAge exceeded chronological age by 8.8 and 2.3 years in the EUPD and control group, respectively. Similarly, EAA marker AgeAccelGrim was substantially higher in EUPD subjects when compared to controls, in both univariate and multivariate analyzes (p < 0.00001). Tobacco usage conferred substantial within-group effects on the EA-chronological age difference, i.e., 10.74 years (SD = 4.19) compared to 6.00 years (SD = 3.10) in the non-user EUPD group (p < 0.00001). Notably, past alcohol and substance abuse, use of psychotropic medications, global assessment of functioning, self-reported exposure to violent behavior in youth and adulthood, later completed suicide (N = 8) and age at first suicide attempt did not predict EAA in the EUPD group (p > 0.05). These results underscore the importance of addressing medical health conditions along with low-cost preventative interventions aimed at improving somatic health outcomes in EUPD, such as efforts to support cessation of tobacco use. The independency of GrimAge to other EA algorithms in this group of severely impaired EUPD patients, suggest it may have unique characteristics to evaluate risk of adverse health outcomes in context of psychiatric disorders.", "doi": "10.1038/s41398-023-02369-7", "pmid": "36813766", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "NGI SNP genotyping": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41398-023-02369-7"}, {"db": "pmc", "key": "PMC9946998"}], "notes": [], "created": "2023-02-24T13:14:04.756Z", "modified": "2023-02-24T13:14:04.784Z"}, {"entity": "publication", "iuid": "93dff8562c4a43bf9052f0be7d1f2716", "links": {"self": {"href": "https://publications.scilifelab.se/publication/93dff8562c4a43bf9052f0be7d1f2716.json"}, "display": {"href": "https://publications.scilifelab.se/publication/93dff8562c4a43bf9052f0be7d1f2716"}}, "title": "Meta-analysis of genome-wide association studies of hoarding symptoms in 27,537 individuals.", "authors": [{"family": "Strom", "given": "Nora I", "initials": "NI", "orcid": "0000-0002-5261-8852", "researcher": {"href": "https://publications.scilifelab.se/researcher/bcd18b76d8d948dfb5529a2be294ecab.json"}}, {"family": "Smit", "given": "Dirk J A", "initials": "DJA", "orcid": "0000-0001-8301-8860", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe64f7980537495aba79c0eca978e95d.json"}}, {"family": "Silzer", "given": "Talisa", "initials": "T"}, {"family": "Iyegbe", "given": "Conrad", "initials": "C"}, {"family": "Burton", "given": "Christie L", "initials": "CL", "orcid": "0000-0002-8955-6528", "researcher": {"href": "https://publications.scilifelab.se/researcher/4607f407ac9d4213a81b4a77b4cce4ad.json"}}, {"family": "Pool", "given": "Ren\u00e9", "initials": "R", "orcid": "0000-0001-5579-0933", "researcher": {"href": "https://publications.scilifelab.se/researcher/fc33e91c50654a6a88a44db4b6755f73.json"}}, {"family": "Lemire", "given": "Mathieu", "initials": "M"}, {"family": "Crowley", "given": "James J", "initials": "JJ", "orcid": "0000-0001-9051-1557", "researcher": {"href": "https://publications.scilifelab.se/researcher/14ecad66262b47dcadebcc8c7e759024.json"}}, {"family": "Hottenga", "given": "Jouke-Jan", "initials": "JJ", "orcid": "0000-0002-5668-2368", "researcher": {"href": "https://publications.scilifelab.se/researcher/75553b594b1f4255833de730f7f7d170.json"}}, {"family": "Ivanov", "given": "Volen Z", "initials": "VZ"}, {"family": "Larsson", "given": "Henrik", "initials": "H", "orcid": "0000-0002-6851-3297", "researcher": {"href": "https://publications.scilifelab.se/researcher/21f2cca2f6b74c5393c0fc33bcf15ee6.json"}}, {"family": "Lichtenstein", "given": "Paul", "initials": "P", "orcid": "0000-0003-3037-5287", "researcher": {"href": "https://publications.scilifelab.se/researcher/4db67c51837b4cdfa18cacbc3fca1173.json"}}, {"family": "Magnusson", "given": "Patrik", "initials": "P", "orcid": "0000-0002-7315-7899", "researcher": {"href": "https://publications.scilifelab.se/researcher/b277b6387de142bbab91fad82d9eff09.json"}}, {"family": "R\u00fcck", "given": "Christian", "initials": "C", "orcid": "0000-0002-8742-0168", "researcher": {"href": "https://publications.scilifelab.se/researcher/496a782babf3403ba32f805f360d246f.json"}}, {"family": "Schachar", "given": "Russell J", "initials": "RJ"}, {"family": "Wu", "given": "Hei Man", "initials": "HM", "orcid": "0000-0003-1559-7586", "researcher": {"href": "https://publications.scilifelab.se/researcher/1578fafcb32642609d408fcff09cd91e.json"}}, {"family": "Meier", "given": "Sandra M", "initials": "SM"}, {"family": "Crosbie", "given": "Jennifer", "initials": "J"}, {"family": "Arnold", "given": "Paul D", "initials": "PD", "orcid": "0000-0003-2496-4624", "researcher": {"href": "https://publications.scilifelab.se/researcher/c21fa35b3bf246ab8a96866510fc069b.json"}}, {"family": "Mattheisen", "given": "Manuel", "initials": "M", "orcid": "0000-0002-8442-493X", "researcher": {"href": "https://publications.scilifelab.se/researcher/c38fef539c2c4cebb81eff917aa3d4ef.json"}}, {"family": "Boomsma", "given": "Dorret I", "initials": "DI", "orcid": "0000-0002-7099-7972", "researcher": {"href": "https://publications.scilifelab.se/researcher/4b66ab2525fd4a468e7a4ad14c955cb4.json"}}, {"family": "Mataix-Cols", "given": "David", "initials": "D", "orcid": "0000-0002-4545-0924", "researcher": {"href": "https://publications.scilifelab.se/researcher/9954431e50b749aeb6957835ae1632f3.json"}}, {"family": "Cath", "given": "Danielle", "initials": "D"}], "type": "meta-analysis", "published": "2022-11-15", "journal": {"title": "Transl Psychiatry", "issn": "2158-3188", "volume": "12", "issue": "1", "pages": "479", "issn-l": "2158-3188"}, "abstract": "Hoarding Disorder (HD) is a mental disorder characterized by persistent difficulties discarding or parting with possessions, often resulting in cluttered living spaces, distress, and impairment. Its etiology is largely unknown, but twin studies suggest that it is moderately heritable. In this study, we pooled phenotypic and genomic data from seven international cohorts (N = 27,537 individuals) and conducted a genome wide association study (GWAS) meta-analysis of parent- or self-reported hoarding symptoms (HS). We followed up the results with gene-based and gene-set analyses, as well as leave-one-out HS polygenic risk score (PRS) analyses. To examine a possible genetic association between hoarding symptoms and other phenotypes we conducted cross-trait PRS analyses. Though we did not report any genome-wide significant SNPs, we report heritability estimates for the twin-cohorts between 26-48%, and a SNP-heritability of 11% for an unrelated sub-cohort. Cross-trait PRS analyses showed that the genetic risk for schizophrenia and autism spectrum disorder were significantly associated with hoarding symptoms. We also found suggestive evidence for an association with educational attainment. There were no significant associations with other phenotypes previously linked to HD, such as obsessive-compulsive disorder, depression, anxiety, or attention-deficit hyperactivity disorder. To conclude, we found that HS are heritable, confirming and extending previous twin studies but we had limited power to detect any genome-wide significant loci. Much larger samples will be needed to further extend these findings and reach a \"gene discovery zone\". To move the field forward, future research should not only include genetic analyses of quantitative hoarding traits in larger samples, but also in samples of individuals meeting strict diagnostic criteria for HD, and more ethnically diverse samples.", "doi": "10.1038/s41398-022-02248-7", "pmid": "36379924", "labels": {"National Genomics Infrastructure": "Service", "NGI SNP genotyping": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9666541"}, {"db": "pii", "key": "10.1038/s41398-022-02248-7"}], "notes": [], "created": "2022-12-23T11:26:48.889Z", "modified": "2024-01-16T13:48:34.470Z"}, {"entity": "publication", "iuid": "af20ba6362a54f1bb72479cd4ba927c2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/af20ba6362a54f1bb72479cd4ba927c2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/af20ba6362a54f1bb72479cd4ba927c2"}}, "title": "Accelerated epigenetic aging in suicide attempters uninfluenced by high intent-to-die and choice of lethal methods.", "authors": [{"family": "Jokinen", "given": "Jussi", "initials": "J"}, {"family": "Andersson", "given": "Peter", "initials": "P"}, {"family": "Chatzittofis", "given": "Andreas", "initials": "A", "orcid": "0000-0002-6635-9564", "researcher": {"href": "https://publications.scilifelab.se/researcher/35583d0beb824e068ffd9c015d46309d.json"}}, {"family": "Savard", "given": "Josephine", "initials": "J", "orcid": "0000-0002-0140-4109", "researcher": {"href": "https://publications.scilifelab.se/researcher/19be5afe66ea42d5a2d5cb1695ff0da6.json"}}, {"family": "Rask-Andersen", "given": "Mathias", "initials": "M"}, {"family": "\u00c5sberg", "given": "Marie", "initials": "M"}, {"family": "Bostr\u00f6m", "given": "Adrian Desai E", "initials": "ADE", "orcid": "0000-0001-8604-9638", "researcher": {"href": "https://publications.scilifelab.se/researcher/5ace74b9a4894d82a16e7ff445bbcea6.json"}}], "type": "journal article", "published": "2022-06-02", "journal": {"title": "Transl Psychiatry", "issn": "2158-3188", "volume": "12", "issue": "1", "pages": "224", "issn-l": "2158-3188"}, "abstract": "Suicide attempts (SA) are associated with excess non-suicidal mortality, putatively mediated in part by premature cellular senescence. Epigenetic age (EA) estimators of biological age have been previously demonstrated to strongly predict physiological dysregulation and mortality risk. Herein, we investigate if violent SA with high intent-to-die is predictive of epigenetics-derived estimates of biological aging. The genome-wide methylation pattern was measured using the Illumina Infinium Methylation EPIC BeadChip in whole blood of 88 suicide attempters. Subjects were stratified into two groups based on the putative risk of later committed suicide (low- [n = 58] and high-risk [n = 30]) in dependency of SA method (violent or non-violent) and/or intent-to-die (high/low). Estimators of intrinsic and extrinsic EA acceleration, one marker optimized to predict physiological dysregulation (DNAmPhenoAge/AgeAccelPheno) and one optimized to predict lifespan (DNAmGrimAge/AgeAccelGrim) were investigated for associations to severity of SA, by univariate and multivariate analyses. The study was adequately powered to detect differences of 2.2 years in AgeAccelGrim in relation to SA severity. Baseline DNAmGrimAge exceeded chronological age by 7.3 years on average across all samples, conferring a mean 24.6% increase in relation to actual age. No individual EA acceleration marker was differentiated by suicidal risk group (p > 0.1). Thus, SA per se but not severity of SA is related to EA, implicating that excess non-suicidal mortality in SA is unrelated to risk of committed suicide. Preventative healthcare efforts aimed at curtailing excess mortality after SA may benefit from acting equally powerful to recognize somatic comorbidities irrespective of the severity inherent in the act itself.", "doi": "10.1038/s41398-022-01998-8", "pmid": "35654772", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "NGI SNP genotyping": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41398-022-01998-8"}], "notes": [], "created": "2022-06-14T13:16:27.182Z", "modified": "2022-06-14T13:16:27.377Z"}, {"entity": "publication", "iuid": "9e09f16235bb47098747041ff56dd562", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9e09f16235bb47098747041ff56dd562.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9e09f16235bb47098747041ff56dd562"}}, "title": "Genetics of age-at-onset in major depression.", "authors": [{"family": "Harder", "given": "Arvid", "initials": "A"}, {"family": "Nguyen", "given": "Thuy-Dung", "initials": "TD"}, {"family": "Pasman", "given": "Jo\u00eblle A", "initials": "JA"}, {"family": "Mosing", "given": "Miriam A", "initials": "MA"}, {"family": "H\u00e4gg", "given": "Sara", "initials": "S", "orcid": "0000-0002-2452-1500", "researcher": {"href": "https://publications.scilifelab.se/researcher/e1d010dfe5d84a33b6a6c7ec815ca3dc.json"}}, {"family": "Lu", "given": "Yi", "initials": "Y", "orcid": "0000-0001-9933-3654", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a73eafe0b0e4221a77b96800883413d.json"}}], "type": "journal article", "published": "2022-03-26", "journal": {"title": "Transl Psychiatry", "issn": "2158-3188", "volume": "12", "issue": "1", "pages": "124", "issn-l": "2158-3188"}, "abstract": "Major depression (MD) is a complex, heterogeneous neuropsychiatric disorder. An early age at onset of major depression (AAO-MD) has been associated with more severe illness, psychosis, and suicidality. However, not much is known about what contributes to individual variation in this important clinical characteristic. This study sought to investigate the genetic components underlying AAO-MD. To investigate the genetics of AAO-MD, we conducted a genome-wide association meta-analysis of AAO-MD based on self-reported age of symptoms onset and self-reported age at first diagnosis from the UK Biobank cohort (total N = 94,154). We examined the genetic relationship between AAO-MD and five other psychiatric disorders. Polygenic risk scores were derived to examine their association with five psychiatric outcomes and AAO-MD in independent sub-samples. We found a small but significant SNP-heritability (~6%) for the AAO-MD phenotype. No SNP or gene reached SNP or gene-level significance. We found evidence that AAO-MD has genetic overlap with MD risk ([Formula: see text] = -0.49). Similarly, we found shared genetic risks between AAO-MD and autism-spectrum disorder, schizophrenia, bipolar disorder, and anorexia nervosa ([Formula: see text] range: -0.3 to -0.5). Polygenic risk scores for AAO-MD were associated with MD, schizophrenia, and bipolar disorder, and AAO-MD was in turn associated with polygenic risk scores derived from these disorders. Overall, our results indicate that AAO-MD is heritable, and there is an inverse genetic relationship between AAO-MD and both major depression and other psychiatric disorders, meaning that SNPs associated with earlier age at onset tend to increase the risk for psychiatric disorders. These findings suggest that the genetics of AAO-MD contribute to the shared genetic architecture observed between psychiatric disorders.", "doi": "10.1038/s41398-022-01888-z", "pmid": "35347114", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41398-022-01888-z"}, {"db": "pmc", "key": "PMC8960842"}], "notes": [], "created": "2022-11-09T15:47:48.263Z", "modified": "2024-01-16T13:48:37.225Z"}, {"entity": "publication", "iuid": "fc065ee0769b4b74b7d35c3b218b8338", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fc065ee0769b4b74b7d35c3b218b8338.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fc065ee0769b4b74b7d35c3b218b8338"}}, "title": "A serum proteomic study of two case-control cohorts identifies novel biomarkers for bipolar disorder.", "authors": [{"family": "G\u00f6teson", "given": "Andreas", "initials": "A", "orcid": "0000-0001-6118-6054", "researcher": {"href": "https://publications.scilifelab.se/researcher/ddb9372de0984261bce8b2ebdeee26ee.json"}}, {"family": "Isgren", "given": "Anniella", "initials": "A"}, {"family": "Sparding", "given": "Timea", "initials": "T"}, {"family": "Holm\u00e9n-Larsson", "given": "Jessica", "initials": "J"}, {"family": "Jakobsson", "given": "Joel", "initials": "J"}, {"family": "P\u00e5lsson", "given": "Erik", "initials": "E"}, {"family": "Land\u00e9n", "given": "Mikael", "initials": "M", "orcid": "0000-0002-4496-6451", "researcher": {"href": "https://publications.scilifelab.se/researcher/792e2b8b8da94572a4d2815703d29749.json"}}], "type": "journal article", "published": "2022-02-08", "journal": {"title": "Transl Psychiatry", "issn": "2158-3188", "volume": "12", "issue": "1", "pages": "55", "issn-l": "2158-3188"}, "abstract": "We set out to identify novel protein associations with potential as clinically viable biomarkers for bipolar disorder. To this end, we used proximity extension assay to analyze 201 unique proteins in blood serum from two independent cohorts comprising patients with bipolar disorder and healthy controls (total n = 493). We identified 32 proteins significantly associated with bipolar disorder in both case-control cohorts after adjusting for relevant covariates. Twenty-two findings are novel to bipolar disorder, but 10 proteins have previously been associated with bipolar disorder: chitinase-3-like protein 1, C-C motif chemokine 3 (CCL3), CCL4, CCL20, CCL25, interleukin 10, growth/differentiation factor-15, matrilysin (MMP-7), pro-adrenomedullin, and TNF-R1. Next, we estimated the variance in serum protein concentrations explained by psychiatric drugs and found that some case-control associations may have been driven by psychiatric drugs. The highest variance explained was observed between lithium use and MMP-7, and in post-hoc analyses and found that the serum concentration of MMP-7 was positively associated with serum lithium concentration, duration of lithium therapy, and inversely associated with estimated glomerular filtration rate in an interaction with lithium. This is noteworthy given that MMP-7 has been suggested as a mediator of renal tubulointerstitial fibrosis, which is characteristic of lithium-induced nephropathy. Finally, we used machine learning to evaluate the classification performance of the studied biomarkers but the average performance in unseen data was fair to moderate (area under the receiver operating curve = 0.72). Taken together, our serum biomarker findings provide novel insight to the etiopathology of bipolar disorder, and we present a suggestive biomarker for lithium-induced nephropathy.", "doi": "10.1038/s41398-022-01819-y", "pmid": "35136035", "labels": {"Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8826439"}, {"db": "pii", "key": "10.1038/s41398-022-01819-y"}], "notes": [], "created": "2022-12-02T08:52:29.546Z", "modified": "2022-12-02T08:52:29.584Z"}, {"entity": "publication", "iuid": "1d1abfbe6bf14f89a16e62a59302a18f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1d1abfbe6bf14f89a16e62a59302a18f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1d1abfbe6bf14f89a16e62a59302a18f"}}, "title": "Autoantibody profiles associated with clinical features in psychotic disorders.", "authors": [{"family": "Jernbom Falk", "given": "August", "initials": "A", "orcid": "0000-0002-7773-1851", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe6400bde68b46899515cef5bea05fca.json"}}, {"family": "Galletly", "given": "Cherrie", "initials": "C", "orcid": "0000-0001-6185-9677", "researcher": {"href": "https://publications.scilifelab.se/researcher/eadd383f017b42378128e92766c3d451.json"}}, {"family": "Just", "given": "David", "initials": "D", "orcid": "0000-0001-6126-2256", "researcher": {"href": "https://publications.scilifelab.se/researcher/46f687d3a9cf4400932c75510807c764.json"}}, {"family": "Toben", "given": "Catherine", "initials": "C"}, {"family": "Baune", "given": "Bernhard T", "initials": "BT"}, {"family": "Clark", "given": "Scott R", "initials": "SR", "orcid": "0000-0003-1640-5611", "researcher": {"href": "https://publications.scilifelab.se/researcher/6d99798c02a2436ea76de86f381750b4.json"}}, {"family": "Liu", "given": "Dennis", "initials": "D"}, {"family": "Nilsson", "given": "Peter", "initials": "P", "orcid": "0000-0002-4657-8532", "researcher": {"href": "https://publications.scilifelab.se/researcher/799bcf1cf8cf451296f4535dd4ca9dc0.json"}}, {"family": "M\u00e5nberg", "given": "Anna", "initials": "A", "orcid": "0000-0002-0056-1313", "researcher": {"href": "https://publications.scilifelab.se/researcher/6d155273b5b54e61b773f263e4f2ce9b.json"}}, {"family": "Schubert", "given": "K Oliver", "initials": "KO", "orcid": "0000-0003-1690-0209", "researcher": {"href": "https://publications.scilifelab.se/researcher/740bdd06c28b47f9bfcc37a1e3e084bf.json"}}], "type": "journal article", "published": "2021-09-13", "journal": {"title": "Transl Psychiatry", "issn": "2158-3188", "issn-l": "2158-3188", "volume": "11", "issue": "1", "pages": "474"}, "abstract": "Autoimmune processes are suspected to play a role in the pathophysiology of psychotic disorders. Better understanding of the associations between auto-immunoglobulin G (IgG) repertoires and clinical features of mental illness could yield novel models of the pathophysiology of psychosis, and markers for biological patient stratification. We undertook cross-sectional detection and quantification of auto-IgGs in peripheral blood plasma of 461 people (39% females) with established psychotic disorder diagnoses. Broad screening of 24 individuals was carried out on group level in eight clinically defined groups using planar protein microarrays containing 42,100 human antigens representing 18,914 proteins. Autoantibodies indicated by broad screening and in the previous literature were measured using a 380-plex bead-based array for autoantibody profiling of all 461 individuals. Associations between autoantibody profiles and dichotomized clinical characteristics were assessed using a stepwise selection procedure. Broad screening and follow-up targeted analyses revealed highly individual autoantibody profiles. Females, and people with family histories of obesity or of psychiatric disorders other than schizophrenia had the highest overall autoantibody counts. People who had experienced subjective thought disorder and/or were treated with clozapine (trend) had the lowest overall counts. Furthermore, six autoantibodies were associated with specific psychopathology symptoms: anti-AP3B2 (persecutory delusions), anti-TDO2 (hallucinations), anti-CRYGN (initial insomnia); anti-APMAP (poor appetite), anti-OLFM1 (above-median cognitive function), and anti-WHAMMP3 (anhedonia and dysphoria). Future studies should clarify whether there are causal biological relationships, and whether autoantibodies could be used as clinical markers to inform diagnostic patient stratification and choice of treatment.", "doi": "10.1038/s41398-021-01596-0", "pmid": "34518517", "labels": {"Autoimmunity and Serology Profiling": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41398-021-01596-0"}, {"db": "pmc", "key": "PMC8438048"}], "notes": [], "created": "2021-09-15T10:19:31.008Z", "modified": "2021-12-09T13:48:43.908Z"}, {"entity": "publication", "iuid": "5321d052b82a493991baf82d30627863", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5321d052b82a493991baf82d30627863.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5321d052b82a493991baf82d30627863"}}, "title": "Genetic association study of childhood aggression across raters, instruments, and age.", "authors": [{"family": "Ip", "given": "Hill F", "initials": "HF", "orcid": "0000-0003-1991-5019", "researcher": {"href": "https://publications.scilifelab.se/researcher/b04deeb54c174ad5aaed5247d9303dd2.json"}}, {"family": "van der Laan", "given": "Camiel M", "initials": "CM"}, {"family": "Krapohl", "given": "Eva M L", "initials": "EML"}, {"family": "Brikell", "given": "Isabell", "initials": "I"}, {"family": "S\u00e1nchez-Mora", "given": "Cristina", "initials": "C", "orcid": "0000-0003-4211-1107", "researcher": {"href": "https://publications.scilifelab.se/researcher/b191e52b7d984841a81f05d77f7e0d08.json"}}, {"family": "Nolte", "given": "Ilja M", "initials": "IM", "orcid": "0000-0001-5047-4077", "researcher": {"href": "https://publications.scilifelab.se/researcher/abd76becaa8a4df284103c3e20261f10.json"}}, {"family": "St Pourcain", "given": "Beate", "initials": "B", "orcid": "0000-0002-4680-3517", "researcher": {"href": "https://publications.scilifelab.se/researcher/d5cfdc61a13f46589373c8c4b5a15a47.json"}}, {"family": "Bolhuis", "given": "Koen", "initials": "K"}, {"family": "Palviainen", "given": "Teemu", "initials": "T", "orcid": "0000-0002-7847-8384", "researcher": {"href": "https://publications.scilifelab.se/researcher/bcbc4c92052b4819b5d7d821c0c421b0.json"}}, {"family": "Zafarmand", "given": "Hadi", "initials": "H"}, {"family": "Colodro-Conde", "given": "Luc\u00eda", "initials": "L", "orcid": "0000-0002-9004-364X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a3d04cc447a34470a5063ae581eb9030.json"}}, {"family": "Gordon", "given": "Scott", "initials": "S", "orcid": "0000-0001-7623-328X", "researcher": {"href": "https://publications.scilifelab.se/researcher/8815739662214e75b60f71f0b1ca58a6.json"}}, {"family": "Zayats", "given": "Tetyana", "initials": "T"}, {"family": "Aliev", "given": "Fazil", "initials": "F", "orcid": "0000-0001-8357-4699", "researcher": {"href": "https://publications.scilifelab.se/researcher/85556629452a4054bf7228b5f7049811.json"}}, {"family": "Jiang", "given": "Chang", "initials": "C"}, {"family": "Wang", "given": "Carol A", "initials": "CA"}, {"family": "Saunders", "given": "Gretchen", "initials": "G"}, {"family": "Karhunen", "given": "Ville", "initials": "V", "orcid": "0000-0001-6064-1588", "researcher": {"href": "https://publications.scilifelab.se/researcher/219a89cb373447218073a1f58fb77864.json"}}, {"family": "Hammerschlag", "given": "Anke R", "initials": "AR"}, {"family": "Adkins", "given": "Daniel E", "initials": "DE"}, {"family": "Border", "given": "Richard", "initials": "R", "orcid": "0000-0002-6293-2968", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a0382c1a2bb4c0ca9e9c2256b0ce00b.json"}}, {"family": "Peterson", "given": "Roseann E", "initials": "RE"}, {"family": "Prinz", "given": "Joseph A", "initials": "JA"}, {"family": "Thiering", "given": "Elisabeth", "initials": "E"}, {"family": "Sepp\u00e4l\u00e4", "given": "Ilkka", "initials": "I"}, {"family": "Vilor-Tejedor", "given": "Nat\u00e0lia", "initials": "N"}, {"family": "Ahluwalia", "given": "Tarunveer S", "initials": "TS", "orcid": "0000-0002-7464-3354", "researcher": {"href": "https://publications.scilifelab.se/researcher/2fde142189574b44a72155785763a327.json"}}, {"family": "Day", "given": "Felix R", "initials": "FR", "orcid": "0000-0003-3789-7651", "researcher": {"href": "https://publications.scilifelab.se/researcher/5d9ffc4d251a4469bcb97dd24dcc4218.json"}}, {"family": "Hottenga", "given": "Jouke-Jan", "initials": "J"}, {"family": "Allegrini", "given": "Andrea G", "initials": "AG"}, {"family": "Rimfeld", "given": "Kaili", "initials": "K", "orcid": "0000-0001-5139-065X", "researcher": {"href": "https://publications.scilifelab.se/researcher/660709eb850544ba8c84fbc86cb53ac6.json"}}, {"family": "Chen", "given": "Qi", "initials": "Q"}, {"family": "Lu", "given": "Yi", "initials": "Y", "orcid": "0000-0001-9933-3654", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a73eafe0b0e4221a77b96800883413d.json"}}, {"family": "Martin", "given": "Joanna", "initials": "J"}, {"family": "Soler Artigas", "given": "Mar\u00eda", "initials": "M", "orcid": "0000-0002-3213-1107", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e0e1e065b024da28acc1e1e0d14c773.json"}}, {"family": "Rovira", "given": "Paula", "initials": "P"}, {"family": "Bosch", "given": "Rosa", "initials": "R", "orcid": "0000-0002-7596-183X", "researcher": {"href": "https://publications.scilifelab.se/researcher/86bdf80d16c34257b4aa6742ff396c89.json"}}, {"family": "Espa\u00f1ol", "given": "Gemma", "initials": "G"}, {"family": "Ramos Quiroga", "given": "Josep Antoni", "initials": "JA", "orcid": "0000-0003-1622-0350", "researcher": {"href": "https://publications.scilifelab.se/researcher/d301b6f1b0ca48b3a5c8c4b8e07a3984.json"}}, {"family": "Neumann", "given": "Alexander", "initials": "A", "orcid": "0000-0001-6653-3203", "researcher": {"href": "https://publications.scilifelab.se/researcher/e51ca6c997164410957bb8cac445d3e4.json"}}, {"family": "Ensink", "given": "Judith", "initials": "J"}, {"family": "Grasby", "given": "Katrina", "initials": "K", "orcid": "0000-0001-8539-0228", "researcher": {"href": "https://publications.scilifelab.se/researcher/a8e9d35817bc460ea594b892e5d2030e.json"}}, {"family": "Morosoli", "given": "Jos\u00e9 J", "initials": "JJ"}, {"family": "Tong", "given": "Xiaoran", "initials": "X"}, {"family": "Marrington", "given": "Shelby", "initials": "S"}, {"family": "Middeldorp", "given": "Christel", "initials": "C", "orcid": "0000-0002-6218-0428", "researcher": {"href": "https://publications.scilifelab.se/researcher/db38533fb54249b99f1d67d95e19af74.json"}}, {"family": "Scott", "given": "James G", "initials": "JG"}, {"family": "Vinkhuyzen", "given": "Anna", "initials": "A"}, {"family": "Shabalin", "given": "Andrey A", "initials": "AA"}, {"family": "Corley", "given": "Robin", "initials": "R"}, {"family": "Evans", "given": "Luke M", "initials": "LM", "orcid": "0000-0002-7458-1720", "researcher": {"href": "https://publications.scilifelab.se/researcher/ac3c651e69a9455d9e8cb7921afb05d9.json"}}, {"family": "Sugden", "given": "Karen", "initials": "K"}, {"family": "Alemany", "given": "Silvia", "initials": "S", "orcid": "0000-0002-7925-6767", "researcher": {"href": "https://publications.scilifelab.se/researcher/da641b351c9f48fcbd54a186d28806e5.json"}}, {"family": "Sass", "given": "L\u00e6rke", "initials": "L", "orcid": "0000-0002-5217-7014", "researcher": {"href": "https://publications.scilifelab.se/researcher/950b17ef41394606b8023743f86aba1c.json"}}, {"family": "Vinding", "given": "Rebecca", "initials": "R"}, {"family": "Ruth", "given": "Kate", "initials": "K", "orcid": "0000-0003-4966-9170", "researcher": {"href": "https://publications.scilifelab.se/researcher/e5569a5bc7384a75a5a98c2bf04ded7b.json"}}, {"family": "Tyrrell", "given": "Jess", "initials": "J"}, {"family": "Davies", "given": "Gareth E", "initials": "GE"}, {"family": "Ehli", "given": "Erik A", "initials": "EA", "orcid": "0000-0002-7865-3015", "researcher": {"href": "https://publications.scilifelab.se/researcher/16c7ee4d9b20410ba4975ffa49c4b03e.json"}}, {"family": "Hagenbeek", "given": "Fiona A", "initials": "FA", "orcid": "0000-0002-8773-0430", "researcher": {"href": "https://publications.scilifelab.se/researcher/1874bbcb93ed4633879199558ae54877.json"}}, {"family": "De Zeeuw", "given": "Eveline", "initials": "E"}, {"family": "Van Beijsterveldt", "given": "Toos C E M", "initials": "TCEM"}, {"family": "Larsson", "given": "Henrik", "initials": "H"}, {"family": "Snieder", "given": "Harold", "initials": "H", "orcid": "0000-0003-1949-2298", "researcher": {"href": "https://publications.scilifelab.se/researcher/e9276827839a4f3cb50dcaa2ad4708a5.json"}}, {"family": "Verhulst", "given": "Frank C", "initials": "FC"}, {"family": "Amin", "given": "Najaf", "initials": "N"}, {"family": "Whipp", "given": "Alyce M", "initials": "AM"}, {"family": "Korhonen", "given": "Tellervo", "initials": "T"}, {"family": "Vuoksimaa", "given": "Eero", "initials": "E"}, {"family": "Rose", "given": "Richard J", "initials": "RJ"}, {"family": "Uitterlinden", "given": "Andr\u00e9 G", "initials": "AG", "orcid": "0000-0002-7276-3387", "researcher": {"href": "https://publications.scilifelab.se/researcher/273577b238854023a9dffe34dabc3551.json"}}, {"family": "Heath", "given": "Andrew C", "initials": "AC"}, {"family": "Madden", "given": "Pamela", "initials": "P"}, {"family": "Haavik", "given": "Jan", "initials": "J", "orcid": "0000-0001-7865-2808", "researcher": {"href": "https://publications.scilifelab.se/researcher/68db11f9f0c246bdb7cd7943fbdb2af0.json"}}, {"family": "Harris", "given": "Jennifer R", "initials": "JR"}, {"family": "Helgeland", "given": "\u00d8yvind", "initials": "\u00d8"}, {"family": "Johansson", "given": "Stefan", "initials": "S", "orcid": "0000-0002-2298-7008", "researcher": {"href": "https://publications.scilifelab.se/researcher/1b957ea589b342fb9def8ce13ef3bd7e.json"}}, {"family": "Knudsen", "given": "Gun Peggy S", "initials": "GPS", "orcid": "0000-0002-6193-4291", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d14dc1ad847447789b7d9b2176cd972.json"}}, {"family": "Njolstad", "given": "Pal Rasmus", "initials": "PR", "orcid": "0000-0003-0304-6728", "researcher": {"href": "https://publications.scilifelab.se/researcher/7369f0ad21d9406cadc53eec4b05a71b.json"}}, {"family": "Lu", "given": "Qing", "initials": "Q"}, {"family": "Rodriguez", "given": "Alina", "initials": "A", "orcid": "0000-0003-1209-8802", "researcher": {"href": "https://publications.scilifelab.se/researcher/3b887eeb21fe4ebd8e9ab58c409b052a.json"}}, {"family": "Henders", "given": "Anjali K", "initials": "AK"}, {"family": "Mamun", "given": "Abdullah", "initials": "A"}, {"family": "Najman", "given": "Jackob M", "initials": "JM"}, {"family": "Brown", "given": "Sandy", "initials": "S", "orcid": "0000-0001-8780-0323", "researcher": {"href": "https://publications.scilifelab.se/researcher/b7595d4595284a879786dedad90c490b.json"}}, {"family": "Hopfer", "given": "Christian", "initials": "C"}, {"family": "Krauter", "given": "Kenneth", "initials": "K"}, {"family": "Reynolds", "given": "Chandra", "initials": "C"}, {"family": "Smolen", "given": "Andrew", "initials": "A"}, {"family": "Stallings", "given": "Michael", "initials": "M"}, {"family": "Wadsworth", "given": "Sally", "initials": "S"}, {"family": "Wall", "given": "Tamara L", "initials": "TL"}, {"family": "Silberg", "given": "Judy L", "initials": "JL"}, {"family": "Miller", "given": "Allison", "initials": "A", "orcid": "0000-0003-3816-2251", "researcher": {"href": "https://publications.scilifelab.se/researcher/e6311431d086475abc6b2842984202be.json"}}, {"family": "Keltikangas-J\u00e4rvinen", "given": "Liisa", "initials": "L", "orcid": "0000-0002-7977-3852", "researcher": {"href": "https://publications.scilifelab.se/researcher/070ce33c4a654544beaccf943345ef6c.json"}}, {"family": "Hakulinen", "given": "Christian", "initials": "C"}, {"family": "Pulkki-R\u00e5back", "given": "Laura", "initials": "L"}, {"family": "Havdahl", "given": "Alexandra", "initials": "A", "orcid": "0000-0002-9268-0423", "researcher": {"href": "https://publications.scilifelab.se/researcher/27ff8da085f7404c920bad58b6b907a3.json"}}, {"family": "Magnus", "given": "Per", "initials": "P"}, {"family": "Raitakari", "given": "Olli T", "initials": "OT"}, {"family": "Perry", "given": "John R B", "initials": "JRB", "orcid": "0000-0001-6483-3771", "researcher": {"href": "https://publications.scilifelab.se/researcher/39d95b143f6849b1b914bca9563218c8.json"}}, {"family": "Llop", "given": "Sabrina", "initials": "S"}, {"family": "Lopez-Espinosa", "given": "Maria-Jose", "initials": "M"}, {"family": "B\u00f8nnelykke", "given": "Klaus", "initials": "K"}, {"family": "Bisgaard", "given": "Hans", "initials": "H"}, {"family": "Sunyer", "given": "Jordi", "initials": "J"}, {"family": "Lehtim\u00e4ki", "given": "Terho", "initials": "T", "orcid": "0000-0002-2555-4427", "researcher": {"href": "https://publications.scilifelab.se/researcher/03ed59707dae4c8fb9e63ac1f7c398e3.json"}}, {"family": "Arseneault", "given": "Louise", "initials": "L", "orcid": "0000-0002-2938-2191", "researcher": {"href": "https://publications.scilifelab.se/researcher/0664e4afe7de4354924a1b39b87cf570.json"}}, {"family": "Standl", "given": "Marie", "initials": "M"}, {"family": "Heinrich", "given": "Joachim", "initials": "J"}, {"family": "Boden", "given": "Joseph", "initials": "J", "orcid": "0000-0003-1502-1608", "researcher": {"href": "https://publications.scilifelab.se/researcher/3543b6fb1f8e415ebff77901d4f25cbe.json"}}, {"family": "Pearson", "given": "John", "initials": "J", "orcid": "0000-0001-5607-4517", "researcher": {"href": "https://publications.scilifelab.se/researcher/ab30b4696c52461a8b8632d9bf5d0e2d.json"}}, {"family": "Horwood", "given": "L John", "initials": "LJ"}, {"family": "Kennedy", "given": "Martin", "initials": "M", "orcid": "0000-0002-6445-8526", "researcher": {"href": "https://publications.scilifelab.se/researcher/b3ca738758034d28ad823bde5256ffd9.json"}}, {"family": "Poulton", "given": "Richie", "initials": "R", "orcid": "0000-0002-1052-4583", "researcher": {"href": "https://publications.scilifelab.se/researcher/8f61fd90a9804126b169485da8cf65a1.json"}}, {"family": "Eaves", "given": "Lindon J", "initials": "LJ"}, {"family": "Maes", "given": "Hermine H", "initials": "HH"}, {"family": "Hewitt", "given": "John", "initials": "J"}, {"family": "Copeland", "given": "William E", "initials": "WE", "orcid": "0000-0002-1348-7781", "researcher": {"href": "https://publications.scilifelab.se/researcher/751b7c2a826748168fa3eab48fd71bc6.json"}}, {"family": "Costello", "given": "Elizabeth J", "initials": "EJ"}, {"family": "Williams", "given": "Gail M", "initials": "GM"}, {"family": "Wray", "given": "Naomi", "initials": "N", "orcid": "0000-0001-7421-3357", "researcher": {"href": "https://publications.scilifelab.se/researcher/15a175036d9f44f9b4090d7d431f78d7.json"}}, {"family": "J\u00e4rvelin", "given": "Marjo-Riitta", "initials": "M"}, {"family": "McGue", "given": "Matt", "initials": "M", "orcid": "0000-0002-5580-1433", "researcher": {"href": "https://publications.scilifelab.se/researcher/8e55e07667274620b817abebddcbede5.json"}}, {"family": "Iacono", "given": "William", "initials": "W"}, {"family": "Caspi", "given": "Avshalom", "initials": "A"}, {"family": "Moffitt", "given": "Terrie E", "initials": "TE"}, {"family": "Whitehouse", "given": "Andrew", "initials": "A"}, {"family": "Pennell", "given": "Craig E", "initials": "CE", "orcid": "0000-0002-0937-6165", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e35a98141ce4350b6775593f87e40a5.json"}}, {"family": "Klump", "given": "Kelly L", "initials": "KL"}, {"family": "Burt", "given": "S Alexandra", "initials": "SA"}, {"family": "Dick", "given": "Danielle M", "initials": "DM", "orcid": "0000-0002-1636-893X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4b2567011fc84f32a0a1f17c277dbefe.json"}}, {"family": "Reichborn-Kjennerud", "given": "Ted", "initials": "T"}, {"family": "Martin", "given": "Nicholas G", "initials": "NG", "orcid": "0000-0003-4069-8020", "researcher": {"href": "https://publications.scilifelab.se/researcher/1b445e5935f74fd6a71b2e92a9dac176.json"}}, {"family": "Medland", "given": "Sarah E", "initials": "SE", "orcid": "0000-0003-1382-380X", "researcher": {"href": "https://publications.scilifelab.se/researcher/da1f0230a912425c9237830be85aa642.json"}}, {"family": "Vrijkotte", "given": "Tanja", "initials": "T"}, {"family": "Kaprio", "given": "Jaakko", "initials": "J", "orcid": "0000-0002-3716-2455", "researcher": {"href": "https://publications.scilifelab.se/researcher/814d362333844b72a70cba9ebcf61e6f.json"}}, {"family": "Tiemeier", "given": "Henning", "initials": "H", "orcid": "0000-0002-4395-1397", "researcher": {"href": "https://publications.scilifelab.se/researcher/73e05bd74af344ba8d963463f49bb242.json"}}, {"family": "Davey Smith", "given": "George", "initials": "G", "orcid": "0000-0002-1407-8314", "researcher": {"href": "https://publications.scilifelab.se/researcher/0790d5850377432087ad3900af0044e0.json"}}, {"family": "Hartman", "given": "Catharina A", "initials": "CA"}, {"family": "Oldehinkel", "given": "Albertine J", "initials": "AJ", "orcid": "0000-0003-3925-3913", "researcher": {"href": "https://publications.scilifelab.se/researcher/65ee5f9938f547bcbe51cbaf5fd7a9ba.json"}}, {"family": "Casas", "given": "Miquel", "initials": "M"}, {"family": "Ribas\u00e9s", "given": "Marta", "initials": "M", "orcid": "0000-0003-1039-1116", "researcher": {"href": "https://publications.scilifelab.se/researcher/643ddd67f10547c3a68ab3c5cd9ee627.json"}}, {"family": "Lichtenstein", "given": "Paul", "initials": "P", "orcid": "0000-0003-3037-5287", "researcher": {"href": "https://publications.scilifelab.se/researcher/4db67c51837b4cdfa18cacbc3fca1173.json"}}, {"family": "Lundstr\u00f6m", "given": "Sebastian", "initials": "S"}, {"family": "Plomin", "given": "Robert", "initials": "R", "orcid": "0000-0002-0756-3629", "researcher": {"href": "https://publications.scilifelab.se/researcher/26e3ca0c39ff4a5087146d5125e0190f.json"}}, {"family": "Bartels", "given": "Meike", "initials": "M", "orcid": "0000-0002-9667-7555", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a91c095e993411b99e81e21f40d8597.json"}}, {"family": "Nivard", "given": "Michel G", "initials": "MG", "orcid": "0000-0003-2015-1888", "researcher": {"href": "https://publications.scilifelab.se/researcher/0d65d2277e7344a3a13f0d2193c6813b.json"}}, {"family": "Boomsma", "given": "Dorret I", "initials": "DI", "orcid": "0000-0002-7099-7972", "researcher": {"href": "https://publications.scilifelab.se/researcher/4b66ab2525fd4a468e7a4ad14c955cb4.json"}}], "type": "journal article", "published": "2021-07-30", "journal": {"title": "Transl Psychiatry", "issn": "2158-3188", "issn-l": "2158-3188", "volume": "11", "issue": "1", "pages": "413"}, "abstract": "Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGGoverall. The gene-based analysis returned three significant genes: ST3GAL3 (P = 1.6E-06), PCDH7 (P = 2.0E-06), and IPO13 (P = 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from rg = 0.46 between self- and teacher-assessment to rg = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range [Formula: see text]: 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (rg = ~-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range [Formula: see text]: 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.", "doi": "10.1038/s41398-021-01480-x", "pmid": "34330890", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41398-021-01480-x"}, {"db": "pmc", "key": "PMC8324785"}], "notes": [], "created": "2021-08-19T13:42:02.005Z", "modified": "2021-12-07T13:20:40.961Z"}, {"entity": "publication", "iuid": "e0711f8e6d244b13b40907137a87996f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e0711f8e6d244b13b40907137a87996f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e0711f8e6d244b13b40907137a87996f"}}, "title": "Toll-like receptor 4 methylation grade is linked to depressive symptom severity.", "authors": [{"family": "Rasmusson", "given": "Annica J", "initials": "AJ", "orcid": "0000-0002-7228-7755", "researcher": {"href": "https://publications.scilifelab.se/researcher/7ef833f6dd204c189586fba5c33d1d58.json"}}, {"family": "Gallwitz", "given": "Maike", "initials": "M"}, {"family": "Soltanabadi", "given": "Bardia", "initials": "B", "orcid": "0000-0003-4827-5268", "researcher": {"href": "https://publications.scilifelab.se/researcher/5018ceb09cc8462bb8df7b6cad75d615.json"}}, {"family": "Ciuculete", "given": "Diana M", "initials": "DM"}, {"family": "Mengel-From", "given": "Jonas", "initials": "J"}, {"family": "Christensen", "given": "Kaare", "initials": "K", "orcid": "0000-0002-5429-5292", "researcher": {"href": "https://publications.scilifelab.se/researcher/e79ea43d09544efc95351b52ac682910.json"}}, {"family": "Nygaard", "given": "Marianne", "initials": "M", "orcid": "0000-0003-0703-2665", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d68eda16735460d81993dc39006d5a5.json"}}, {"family": "Soerensen", "given": "Mette", "initials": "M", "orcid": "0000-0001-5268-3366", "researcher": {"href": "https://publications.scilifelab.se/researcher/712cb1928fdf429ca777a8209b31090d.json"}}, {"family": "Bostr\u00f6m", "given": "Adrian E", "initials": "AE"}, {"family": "Fredriksson", "given": "Robert", "initials": "R"}, {"family": "Freyhult", "given": "Eva", "initials": "E"}, {"family": "Mwinyi", "given": "Jessica", "initials": "J"}, {"family": "Czamara", "given": "Darina", "initials": "D", "orcid": "0000-0001-7381-904X", "researcher": {"href": "https://publications.scilifelab.se/researcher/0e9a8a7d605d4f63a311fc8a211422a6.json"}}, {"family": "Binder", "given": "Elisabeth B", "initials": "EB", "orcid": "0000-0001-7088-6618", "researcher": {"href": "https://publications.scilifelab.se/researcher/0cfb2bf09e9d49ad922bb5c3c252c716.json"}}, {"family": "Schi\u00f6th", "given": "Helgi B", "initials": "HB"}, {"family": "Cunningham", "given": "Janet L", "initials": "JL", "orcid": "0000-0001-7876-7779", "researcher": {"href": "https://publications.scilifelab.se/researcher/3ab30dd6c6874bc7a227a8699c4a7085.json"}}], "type": "journal article", "published": "2021-06-24", "journal": {"title": "Transl Psychiatry", "issn": "2158-3188", "issn-l": "2158-3188", "volume": "11", "issue": "1", "pages": "371"}, "abstract": "This study explores potential associations between the methylation of promoter-associated CpG sites of the toll-like receptor (TLR)-family, plasma levels of pro-inflammatory proteins and depressive symptoms in young female psychiatric patients. Ratings of depressive symptoms and blood samples were obtained from 92 young women seeking psychiatric care. Methylation of 32 promoter-associated CpG sites in TLR1 to TLR10 was analysed using the Illumina Infinium Methylation EPIC BeadChip. Expression levels of 91 inflammatory proteins were determined by proximity extension assay. Statistical correlations between depressive state, TLR1-10 methylation and inflammatory proteins were investigated. Four additional cohorts were studied to evaluate the generalizability of the findings. In the discovery cohort, methylation grade of cg05429895 (TLR4) in blood was inversely correlated with depressive symptoms score in young adults. After correction for multiple testing, plasma levels of macrophage inflammatory protein 1\u03b2 (MIP-1\u03b2/CCL4) were associated with both TLR4 methylation and depressive symptom severity. A similar inverse association between TLR4 methylation in blood and affective symptoms score was also found in a cohort of 148 both males and females (<40 years of age) from the Danish Twin Registry. These findings were not, however, replicated in three other external cohorts; which differed from the first two cohorts by a higher age and mixed ethnicities, thus limiting the generalizability of our findings. However, TLR4 methylation inversely correlated with TLR4 mRNA expression in the Danish Twin Study indicating a functional significance of methylation at this particular CpG. Higher depression scores in young Scandinavian adults was associated with decreased methylation of TLR4 in blood.", "doi": "10.1038/s41398-021-01481-w", "pmid": "34226490", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Affinity Proteomics Uppsala": "Service", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC8257733"}, {"db": "pii", "key": "10.1038/s41398-021-01481-w"}], "notes": [], "created": "2021-08-19T13:41:38.152Z", "modified": "2024-01-16T13:48:39.445Z"}, {"entity": "publication", "iuid": "c54fad9a92ff45be90b06c461c2854cb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c54fad9a92ff45be90b06c461c2854cb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c54fad9a92ff45be90b06c461c2854cb"}}, "title": "Exploring autoantibody signatures in brain tissue from patients with severe mental illness.", "authors": [{"family": "Just", "given": "David", "initials": "D", "orcid": "0000-0001-6126-2256", "researcher": {"href": "https://publications.scilifelab.se/researcher/46f687d3a9cf4400932c75510807c764.json"}}, {"family": "M\u00e5nberg", "given": "Anna", "initials": "A", "orcid": "0000-0002-0056-1313", "researcher": {"href": "https://publications.scilifelab.se/researcher/6d155273b5b54e61b773f263e4f2ce9b.json"}}, {"family": "Mitsios", "given": "Nicholas", "initials": "N", "orcid": "0000-0001-6243-4953", "researcher": {"href": "https://publications.scilifelab.se/researcher/38efa44f5ed64192b432d6384584f00d.json"}}, {"family": "Stockmeier", "given": "Craig A", "initials": "CA", "orcid": "0000-0003-1861-1013", "researcher": {"href": "https://publications.scilifelab.se/researcher/89ebb5b73b9a42498192d35aea2d92c5.json"}}, {"family": "Rajkowska", "given": "Grazyna", "initials": "G", "orcid": "0000-0002-4348-4688", "researcher": {"href": "https://publications.scilifelab.se/researcher/4122635fead74359983624753ee365ff.json"}}, {"family": "Uhl\u00e9n", "given": "Mathias", "initials": "M", "orcid": "0000-0002-4858-8056", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff81da3cb0cf4262873b993a1b06798c.json"}}, {"family": "Mulder", "given": "Jan", "initials": "J", "orcid": "0000-0003-3717-5018", "researcher": {"href": "https://publications.scilifelab.se/researcher/a8443b271929476bb2b569e39bae732c.json"}}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Cunningham", "given": "Janet L", "initials": "JL", "orcid": "0000-0001-7876-7779", "researcher": {"href": "https://publications.scilifelab.se/researcher/3ab30dd6c6874bc7a227a8699c4a7085.json"}}, {"family": "Nilsson", "given": "Peter", "initials": "P", "orcid": "0000-0002-4657-8532", "researcher": {"href": "https://publications.scilifelab.se/researcher/799bcf1cf8cf451296f4535dd4ca9dc0.json"}}, {"family": "Carlstr\u00f6m", "given": "Eva Lindholm", "initials": "EL", "orcid": "0000-0001-8055-7826", "researcher": {"href": "https://publications.scilifelab.se/researcher/c433744d926b450097e71784b8bcc27c.json"}}], "type": "journal article", "published": "2020-11-18", "journal": {"title": "Transl Psychiatry", "issn": "2158-3188", "volume": "10", "issue": "1", "pages": "401", "issn-l": "2158-3188"}, "abstract": "In recent years, studies have shown higher prevalence of autoantibodies in patients with schizophrenia compared to healthy individuals. This study applies an untargeted and a targeted affinity proteomics approach to explore and characterize the autoantibody repertoire in brain tissues from 73 subjects diagnosed with schizophrenia and 52 control subjects with no psychiatric or neurological disorders. Selected brain tissue lysates were first explored for IgG reactivity on planar microarrays composed of 11,520 protein fragments representing 10,820 unique proteins. Based on these results of ours and other previous studies of autoantibodies related to psychosis, we selected 226 fragments with an average length of 80 amino acids, representing 127 unique proteins. Tissue-based analysis of IgG reactivities using antigen suspension bead arrays was performed in a multiplex and parallel fashion for all 125 subjects. Among the detected autoantigens, higher IgG reactivity in subjects with schizophrenia, as compared to psychiatrically healthy subjects, was found against the glutamate ionotropic receptor NMDA type subunit 2D (anti-GluN2D). In a separate cohort with serum samples from 395 young adults with a wider spectrum of psychiatric disorders, higher levels of serum autoantibodies targeting GluN2D were found when compared to 102 control individuals. By further validating GluN2D and additional potential autoantigens, we will seek insights into how these are associated with severe mental illnesses.", "doi": "10.1038/s41398-020-01079-8", "pmid": "33208725", "labels": {"Autoimmunity and Serology Profiling": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41398-020-01079-8"}, {"db": "pmc", "key": "PMC7676257"}], "notes": [], "created": "2020-11-19T10:26:29.658Z", "modified": "2021-11-10T12:45:09.790Z"}, {"entity": "publication", "iuid": "8278837d4b3745bab6470962fe1dc162", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8278837d4b3745bab6470962fe1dc162.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8278837d4b3745bab6470962fe1dc162"}}, "title": "Identification of candidate genetic variants and altered protein expression in neural stem and mature neural cells support altered microtubule function to be an essential component in bipolar disorder.", "authors": [{"family": "Truv\u00e9", "given": "Katarina", "initials": "K", "orcid": "0000-0002-2449-8283", "researcher": {"href": "https://publications.scilifelab.se/researcher/0c36d2ff5111435aa23416cdfc359b2d.json"}}, {"family": "Parris", "given": "Toshima Z", "initials": "TZ", "orcid": "0000-0003-0834-5540", "researcher": {"href": "https://publications.scilifelab.se/researcher/0d528a2bce6c40829c1a6fed69c9f9ef.json"}}, {"family": "Vizlin-Hodzic", "given": "Dzeneta", "initials": "D", "orcid": "0000-0002-9696-7982", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a86a4c8b32a4af8a90240d44504b32b.json"}}, {"family": "Salmela", "given": "Susanne", "initials": "S"}, {"family": "Berger", "given": "Evelin", "initials": "E"}, {"family": "\u00c5gren", "given": "Hans", "initials": "H", "orcid": "0000-0003-0847-6700", "researcher": {"href": "https://publications.scilifelab.se/researcher/51b06f6b0b8d48fcabe31e6eaf1a08ce.json"}}, {"family": "Funa", "given": "Keiko", "initials": "K"}], "type": "journal article", "published": "2020-11-09", "journal": {"title": "Transl Psychiatry", "issn": "2158-3188", "issn-l": "2158-3188", "volume": "10", "issue": "1", "pages": "390"}, "abstract": "Identification of causative genetic variants leading to the development of bipolar disorder (BD) could result in genetic tests that would facilitate diagnosis. A better understanding of affected genes and pathways is also necessary for targeting of genes that may improve treatment strategies. To date several susceptibility genes have been reported from genome-wide association studies (GWAS), but little is known about specific variants that affect disease development. Here, we performed quantitative proteomics and whole-genome sequencing (WGS). Quantitative proteomics revealed NLRP2 as the most significantly up-regulated protein in neural stem cells and mature neural cells obtained from BD-patient cell samples. These results are in concordance with our previously published transcriptome analysis. Furthermore, the levels of FEZ2 and CADM2 proteins were also significantly differentially expressed in BD compared to control derived cells. The levels of FEZ2 were significantly downregulated in neural stem cells (NSC) while CADM2 was significantly up-regulated in mature neuronal cell culture. Promising novel candidate mutations were identified in the ANK3, NEK3, NEK7, TUBB, ANKRD1, and BRD2 genes. A literature search of candidate variants and deregulated proteins revealed that there are several connections to microtubule function for the molecules putatively involved. Microtubule function in neurons is critical for axon structure and axonal transport. A functional dynamic microtubule is also needed for an advocate response to cellular and environmental stress. If microtubule dynamics is compromised by mutations, it could be followed by deregulated expression forming a possible explanation for the inherited vulnerability to stressful life events that have been proposed to trigger mood episodes in BD patients.", "doi": "10.1038/s41398-020-01056-1", "pmid": "33168801", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41398-020-01056-1"}, {"db": "pmc", "key": "PMC7652854"}], "notes": [], "created": "2020-12-07T16:38:26.771Z", "modified": "2024-01-16T13:48:41.392Z"}, {"entity": "publication", "iuid": "b0d422e67e22439cba7da9453032ef86", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b0d422e67e22439cba7da9453032ef86.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b0d422e67e22439cba7da9453032ef86"}}, "title": "Presynaptic dysfunction in CASK-related neurodevelopmental disorders.", "authors": [{"family": "Becker", "given": "Martin", "initials": "M", "orcid": "0000-0001-8442-4246", "researcher": {"href": "https://publications.scilifelab.se/researcher/85eaa4173364473d83506125206a7193.json"}}, {"family": "Mastropasqua", "given": "Francesca", "initials": "F"}, {"family": "Reising", "given": "Jan Philipp", "initials": "JP"}, {"family": "Maier", "given": "Simon", "initials": "S"}, {"family": "Ho", "given": "Mai-Lan", "initials": "ML"}, {"family": "Rabkina", "given": "Ielyzaveta", "initials": "I"}, {"family": "Li", "given": "Danyang", "initials": "D"}, {"family": "Neufeld", "given": "Janina", "initials": "J", "orcid": "0000-0002-7743-526X", "researcher": {"href": "https://publications.scilifelab.se/researcher/c82ade7791b24c46818bbef76984a383.json"}}, {"family": "Ballenberger", "given": "Lea", "initials": "L"}, {"family": "Myers", "given": "Lynnea", "initials": "L"}, {"family": "Moritz", "given": "Viveka", "initials": "V"}, {"family": "Kele", "given": "Malin", "initials": "M"}, {"family": "Wincent", "given": "Josephine", "initials": "J"}, {"family": "Willfors", "given": "Charlotte", "initials": "C"}, {"family": "Sitnikov", "given": "Rouslan", "initials": "R"}, {"family": "Herlenius", "given": "Eric", "initials": "E", "orcid": "0000-0002-6859-0620", "researcher": {"href": "https://publications.scilifelab.se/researcher/9d634beec270431a8805e609554ce1c9.json"}}, {"family": "Anderlid", "given": "Britt-Marie", "initials": "BM"}, {"family": "Falk", "given": "Anna", "initials": "A", "orcid": "0000-0003-1634-8610", "researcher": {"href": "https://publications.scilifelab.se/researcher/8b708dfb7f0548589bdee53d6e6b536e.json"}}, {"family": "B\u00f6lte", "given": "Sven", "initials": "S", "orcid": "0000-0002-4579-4970", "researcher": {"href": "https://publications.scilifelab.se/researcher/bead50319cae447f90bcf7658d9edf56.json"}}, {"family": "Tammimies", "given": "Kristiina", "initials": "K", "orcid": "0000-0002-8324-4697", "researcher": {"href": "https://publications.scilifelab.se/researcher/ba19ec07147743c6942ea10c9a92482a.json"}}], "type": "journal article", "published": "2020-09-14", "journal": {"title": "Transl Psychiatry", "issn": "2158-3188", "issn-l": "2158-3188", "volume": "10", "issue": "1", "pages": "312"}, "abstract": "CASK-related disorders are genetically defined neurodevelopmental syndromes. There is limited information about the effects of CASK mutations in human neurons. Therefore, we sought to delineate CASK-mutation consequences and neuronal effects using induced pluripotent stem cell-derived neurons from two mutation carriers. One male case with autism spectrum disorder carried a novel splice-site mutation and a female case with intellectual disability carried an intragenic tandem duplication. We show reduction of CASK protein in maturing neurons from the mutation carriers, which leads to significant downregulation of genes involved in presynaptic development and of CASK protein interactors. Furthermore, CASK-deficient neurons showed decreased inhibitory presynapse size as indicated by VGAT staining, which may alter the excitatory-inhibitory (E/I) balance in developing neural circuitries. Using in vivo magnetic resonance spectroscopy quantification of GABA in the male mutation carrier, we further highlight the possibility to validate in vitro cellular data in the brain. Our data show that future pharmacological and clinical studies on targeting presynapses and E/I imbalance could lead to specific treatments for CASK-related disorders.", "doi": "10.1038/s41398-020-00994-0", "pmid": "32929080", "labels": {"Eukaryotic Single Cell Genomics (ESCG)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41398-020-00994-0"}, {"db": "pmc", "key": "PMC7490425"}], "notes": [], "created": "2021-01-11T13:13:34.637Z", "modified": "2024-01-16T13:48:41.715Z"}, {"entity": "publication", "iuid": "d04554a222c64b18b5a4907124fce362", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d04554a222c64b18b5a4907124fce362.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d04554a222c64b18b5a4907124fce362"}}, "title": "Evidence that genes involved in hedgehog signaling are associated with both bipolar disorder and high BMI.", "authors": [{"family": "Pisanu", "given": "Claudia", "initials": "C"}, {"family": "Williams", "given": "Michael J", "initials": "MJ"}, {"family": "Ciuculete", "given": "Diana M", "initials": "DM"}, {"family": "Olivo", "given": "Gaia", "initials": "G"}, {"family": "Del Zompo", "given": "Maria", "initials": "M"}, {"family": "Squassina", "given": "Alessio", "initials": "A"}, {"family": "Schi\u00f6th", "given": "Helgi B", "initials": "HB"}], "type": "journal article", "published": "2019-11-21", "journal": {"volume": "9", "issn": "2158-3188", "issue": "1", "pages": "315", "title": "Transl Psychiatry", "issn-l": "2158-3188"}, "abstract": "Patients with bipolar disorder (BD) show higher frequency of obesity and type 2 diabetes (T2D), but the underlying genetic determinants and molecular pathways are not well studied. Using large publicly available datasets, we (1) conducted a gene-based analysis using MAGMA to identify genes associated with BD and body mass index (BMI) or T2D and investigated their functional enrichment; and (2) performed two meta-analyses between BD and BMI, as well as BD and T2D using Metasoft. Target druggability was assessed using the Drug Gene Interaction Database (DGIdb). We identified 518 and 390 genes significantly associated with BD and BMI or BD and T2D, respectively. A total of 52 and 12 genes, respectively, were significant after multiple testing correction. Pathway analyses conducted on nominally significant targets showed that genes associated with BD and BMI were enriched for the Neuronal cell body Gene Ontology (GO) term (p = 1.0E-04; false discovery rate (FDR) = 0.025) and different pathways, including the Signaling by Hedgehog pathway (p = 4.8E-05, FDR = 0.02), while genes associated with BD and T2D showed no specific enrichment. The meta-analysis between BD and BMI identified 64 relevant single nucleotide polymorphisms (SNPs). While the majority of these were located in intergenic regions or in a locus on chromosome 16 near and in the NPIPL1 and SH2B1 genes (best SNP: rs4788101, p = 2.1E-24), five were located in the ETV5 gene (best SNP: rs1516725, p = 1E-24), which was previously associated with both BD and obesity, and one in the RPGRIP1L gene (rs1477199, p = 5.7E-09), which was also included in the Signaling by Hedgehog pathway. The meta-analysis between BD and T2D identified six significant SNPs, three of which were located in ALAS1 (best SNP: rs352165, p = 3.4E-08). Thirteen SNPs associated with BD and BMI, and one with BD and T2D, were located in genes which are part of the druggable genome. Our results support the hypothesis of shared genetic determinants between BD and BMI and point to genes involved in Hedgehog signaling as promising targets.", "doi": "10.1038/s41398-019-0652-x", "pmid": "31754094", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41398-019-0652-x"}], "notes": [], "created": "2019-11-28T07:41:33.694Z", "modified": "2024-01-16T13:48:43.483Z"}, {"entity": "publication", "iuid": "d76d3e51f0094752b0b8b525a73f55a8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d76d3e51f0094752b0b8b525a73f55a8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d76d3e51f0094752b0b8b525a73f55a8"}}, "title": "The genomics of major psychiatric disorders in a large pedigree from Northern Sweden.", "authors": [{"family": "Szatkiewicz", "given": "Jin", "initials": "J"}, {"family": "Crowley", "given": "James J", "initials": "JJ"}, {"family": "Adolfsson", "given": "Annelie Nordin", "initials": "AN"}, {"family": "\u00c5berg", "given": "Karolina A", "initials": "KA"}, {"family": "Alaerts", "given": "Maaike", "initials": "M"}, {"family": "Genovese", "given": "Giulio", "initials": "G"}, {"family": "McCarroll", "given": "Steven", "initials": "S"}, {"family": "Del-Favero", "given": "Jurgen", "initials": "J"}, {"family": "Adolfsson", "given": "Rolf", "initials": "R"}, {"family": "Sullivan", "given": "Patrick F", "initials": "PF", "orcid": "0000-0002-6619-873X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4d95de0b5ab14586980a6a13c8299346.json"}}], "type": "journal article", "published": "2019-02-04", "journal": {"volume": "9", "issn": "2158-3188", "issue": "1", "pages": "60", "title": "Transl Psychiatry", "issn-l": "2158-3188"}, "abstract": "We searched for genetic causes of major psychiatric disorders (bipolar disorder, schizoaffective disorder, and schizophrenia) in a large, densely affected pedigree from Northern Sweden that originated with three pairs of founders born around 1650. We applied a systematic genomic approach to the pedigree via karyotyping (N = 9), genome-wide SNP arrays (N = 418), whole-exome sequencing (N = 26), and whole-genome sequencing (N = 10). Comprehensive analysis did not identify plausible variants of strong effect. Rather, pedigree cases had significantly higher genetic risk scores compared to pedigree and community controls.", "doi": "10.1038/s41398-019-0414-9", "pmid": "30718465", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41398-019-0414-9"}, {"db": "pmc", "key": "PMC6362018"}], "notes": [], "created": "2019-04-23T09:58:54.570Z", "modified": "2024-01-16T13:48:44.705Z"}, {"entity": "publication", "iuid": "216ae64b6c9f43328ad351f4c4320330", "links": {"self": {"href": "https://publications.scilifelab.se/publication/216ae64b6c9f43328ad351f4c4320330.json"}, "display": {"href": "https://publications.scilifelab.se/publication/216ae64b6c9f43328ad351f4c4320330"}}, "title": "Untargeted screening for novel autoantibodies with prognostic value in first-episode psychosis.", "authors": [{"family": "Zandian", "given": "A", "initials": "A"}, {"family": "Wing\u00e5rd", "given": "L", "initials": "L"}, {"family": "Nilsson", "given": "H", "initials": "H"}, {"family": "Sj\u00f6stedt", "given": "E", "initials": "E"}, {"family": "Johansson", "given": "D X", "initials": "DX"}, {"family": "Just", "given": "D", "initials": "D"}, {"family": "Hellstr\u00f6m", "given": "C", "initials": "C"}, {"family": "Uhl\u00e9n", "given": "M", "initials": "M", "orcid": "0000-0002-4858-8056", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff81da3cb0cf4262873b993a1b06798c.json"}}, {"family": "Schwenk", "given": "J M", "initials": "JM", "orcid": "0000-0001-8141-8449", "researcher": {"href": "https://publications.scilifelab.se/researcher/aba5822711b246b397fffacb7ae403b3.json"}}, {"family": "H\u00e4ggmark-M\u00e5nberg", "given": "A", "initials": "A"}, {"family": "Norbeck", "given": "O", "initials": "O"}, {"family": "Owe-Larsson", "given": "B", "initials": "B"}, {"family": "Nilsson", "given": "P", "initials": "P", "orcid": "0000-0002-4657-8532", "researcher": {"href": "https://publications.scilifelab.se/researcher/799bcf1cf8cf451296f4535dd4ca9dc0.json"}}, {"family": "Persson", "given": "M A A", "initials": "MAA"}], "type": "journal article", "published": "2017-07-25", "journal": {"volume": "7", "issn": "2158-3188", "issue": "7", "pages": "e1177", "title": "Transl Psychiatry", "issn-l": "2158-3188"}, "abstract": "Immunological and inflammatory reactions have been suggested to have a role in the development of schizophrenia, a hypothesis that has recently been supported by genetic data. The aim of our study was to perform an unbiased search for autoantibodies in patients with a first psychotic episode, and to explore the association between any seroreactivity and the development of a Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) disorder characterized by chronic or relapsing psychotic symptoms. We collected plasma samples from 53 patients when they were treated for their first-episode psychosis, and 41 non-psychotic controls, after which the patients were followed for a mean duration of 7 years. Thirty patients were diagnosed with schizophrenia, delusional disorder, schizoaffective disorder, bipolar disorder or a long-term unspecified nonorganic psychosis during follow-up, whereas 23 patients achieved complete remission. At the end of follow-up, plasma samples were analyzed for IgG reactivity to 2304 fragments of human proteins using a multiplexed affinity proteomic technique. Eight patient samples showed autoreactivity to the N-terminal fragment of the PAGE (P antigen) protein family (PAGE2B/PAGE2/PAGE5), whereas no such autoreactivity was seen among the controls. PAGE autoreactivity was associated with a significantly increased risk of being diagnosed with schizophrenia during follow-up (odds ratio 6.7, relative risk 4.6). An immunohistochemistry analysis using antisera raised against the N-terminal fragment stained an unknown extracellular target in human cortical brain tissue. Our findings suggest that autoreactivity to the N-terminal portion of the PAGE protein family is associated with schizophrenia in a subset of patients with first-episode psychosis.", "doi": "10.1038/tp.2017.160", "pmid": "28742074", "labels": {"Tissue Profiling": "Collaborative", "Autoimmunity and Serology Profiling": "Collaborative"}, "xrefs": [{"db": "pii", "key": "tp2017160"}, {"db": "pmc", "key": "PMC5538130"}], "notes": [], "created": "2017-11-02T11:35:53.436Z", "modified": "2021-07-08T13:44:33.083Z"}, {"entity": "publication", "iuid": "1d8f9559700447cb85c24a82a88e4d3d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1d8f9559700447cb85c24a82a88e4d3d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1d8f9559700447cb85c24a82a88e4d3d"}}, "title": "Genetic susceptibility to cardiovascular disease and risk of dementia.", "authors": [{"family": "Karlsson", "given": "I K", "initials": "IK"}, {"family": "Ploner", "given": "A", "initials": "A"}, {"family": "Song", "given": "C", "initials": "C"}, {"family": "Gatz", "given": "M", "initials": "M"}, {"family": "Pedersen", "given": "N L", "initials": "NL"}, {"family": "H\u00e4gg", "given": "S", "initials": "S"}], "type": "journal article", "published": "2017-05-30", "journal": {"volume": "7", "issn": "2158-3188", "issue": "5", "pages": "e1142", "title": "Transl Psychiatry", "issn-l": "2158-3188"}, "abstract": "Several studies have shown cardiovascular disease (CVD) to be associated with dementia, but it is not clear whether CVD per se increases the risk of dementia or whether the association is due to shared risk factors. We tested how a genetic risk score (GRS) for coronary artery disease (CAD) affects dementia risk after CVD in 13 231 Swedish twins. We also utilized summarized genome-wide association data to study genetic overlap between CAD and Alzheimer\u00b4s disease (AD), and additionally between shared risk factors and each disease. There was no direct effect of a CAD GRS on dementia (hazard ratio 0.99, 95% confidence interval (CI): 0.98-1.01). However, the GRS for CAD modified the association between CVD and dementia within 3 years of CVD diagnosis, ranging from a hazard ratio of 1.59 (95% CI: 1.05-2.41) in the first GRS quartile to 1.91 (95% CI: 1.28-2.86) in the fourth GRS quartile. Using summary statistics, we found no genetic overlap between CAD and AD. We did, however, find that both AD and CAD share a significant genetic overlap with lipids, but that the overlap arose from clearly distinct gene clusters. In conclusion, genetic susceptibility to CAD was found to modify the association between CVD and dementia, most likely through associations with shared risk factors.", "doi": "10.1038/tp.2017.110", "pmid": "28556832", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "tp2017110"}, {"db": "pmc", "key": "PMC5534941"}], "notes": [], "created": "2018-01-09T13:58:11.467Z", "modified": "2021-06-21T15:37:39.117Z"}, {"entity": "publication", "iuid": "5cd81ab25d5347f49efbc2f7906190f7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5cd81ab25d5347f49efbc2f7906190f7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5cd81ab25d5347f49efbc2f7906190f7"}}, "title": "Early onset of inflammation during ontogeny of bipolar disorder: the NLRP2 inflammasome gene distinctly differentiates between patients and healthy controls in the transition between iPS cell and neural stem cell stages", "authors": [{"family": "Vizlin-Hodzic", "given": "D", "initials": "D"}, {"family": "Zhai", "given": "Q", "initials": "Q"}, {"family": "Illes", "given": "S", "initials": "S"}, {"family": "S\u00f6dersten", "given": "K", "initials": "K"}, {"family": "Truv\u00e9", "given": "K", "initials": "K"}, {"family": "Parris", "given": "T Z", "initials": "TZ"}, {"family": "Sobhan", "given": "P K", "initials": "PK"}, {"family": "Salmela", "given": "S", "initials": "S"}, {"family": "Kosalai", "given": "S T", "initials": "ST"}, {"family": "Kanduri", "given": "C", "initials": "C"}, {"family": "Strandberg", "given": "J", "initials": "J"}, {"family": "Seth", "given": "H", "initials": "H"}, {"family": "Bontell", "given": "T O", "initials": "TO"}, {"family": "Hanse", "given": "E", "initials": "E"}, {"family": "\u00c5gren", "given": "H", "initials": "H"}, {"family": "Funa", "given": "K", "initials": "K"}], "type": "journal-article", "published": "2017-01-24", "journal": {"volume": "7", "issn": "2158-3188", "issue": "1", "pages": "e1010", "title": "Transl Psychiatry", "issn-l": "2158-3188"}, "abstract": null, "doi": "10.1038/tp.2016.284", "pmid": "28117838", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [], "notes": [], "created": "2017-11-01T12:55:00.969Z", "modified": "2020-01-21T13:53:21.828Z"}, {"entity": "publication", "iuid": "b188912bce584c0f99fd1517873a63cd", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b188912bce584c0f99fd1517873a63cd.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b188912bce584c0f99fd1517873a63cd"}}, "title": "A methylome-wide mQTL analysis reveals associations of methylation sites with GAD1 and HDAC3 SNPs and a general psychiatric risk score.", "authors": [{"family": "Ciuculete", "given": "D M", "initials": "DM"}, {"family": "Bostr\u00f6m", "given": "A E", "initials": "AE"}, {"family": "Voisin", "given": "S", "initials": "S"}, {"family": "Philipps", "given": "H", "initials": "H"}, {"family": "Titova", "given": "O E", "initials": "OE"}, {"family": "Bandstein", "given": "M", "initials": "M"}, {"family": "Nikontovic", "given": "L", "initials": "L"}, {"family": "Williams", "given": "M J", "initials": "MJ"}, {"family": "Mwinyi", "given": "J", "initials": "J"}, {"family": "Schi\u00f6th", "given": "H B", "initials": "HB"}], "type": "journal article", "published": "2017-01-17", "journal": {"volume": "7", "issn": "2158-3188", "issue": "1", "pages": "e1002", "title": "Transl Psychiatry", "issn-l": "2158-3188"}, "abstract": "Genome-wide association studies have identified a number of single-nucleotide polymorphisms (SNPs) that are associated with psychiatric diseases. Increasing body of evidence suggests a complex connection of SNPs and the transcriptional and epigenetic regulation of gene expression, which is poorly understood. In the current study, we investigated the interplay between genetic risk variants, shifts in methylation and mRNA levels in whole blood from 223 adolescents distinguished by a risk for developing psychiatric disorders. We analyzed 37 SNPs previously associated with psychiatric diseases in relation to genome-wide DNA methylation levels using linear models, with Bonferroni correction and adjusting for cell-type composition. Associations between DNA methylation, mRNA levels and psychiatric disease risk evaluated by the Development and Well-Being Assessment (DAWBA) score were identified by robust linear models, Pearson's correlations and binary regression models. We detected five SNPs (in HCRTR1, GAD1, HADC3 and FKBP5) that were associated with eight CpG sites, validating five of these SNP-CpG pairs. Three of these CpG sites, that is, cg01089319 (GAD1), cg01089249 (GAD1) and cg24137543 (DIAPH1), manifest in significant gene expression changes and overlap with active regulatory regions in chromatin states of brain tissues. Importantly, methylation levels at cg01089319 were associated with the DAWBA score in the discovery group. These results show how distinct SNPs linked with psychiatric diseases are associated with epigenetic shifts with relevance for gene expression. Our findings give a novel insight on how genetic variants may modulate risks for the development of psychiatric diseases.", "doi": "10.1038/tp.2016.275", "pmid": "28094813", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "tp2016275"}, {"db": "pmc", "key": "PMC5545735"}], "notes": [], "created": "2017-10-25T15:18:15.377Z", "modified": "2024-01-16T13:48:48.687Z"}, {"entity": "publication", "iuid": "ae64983409284d669212f6f04e6402e9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ae64983409284d669212f6f04e6402e9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ae64983409284d669212f6f04e6402e9"}}, "title": "Schizophrenia and subsequent neighborhood deprivation: revisiting the social drift hypothesis using population, twin and molecular genetic data.", "authors": [{"family": "Sariaslan", "given": "A", "initials": "A"}, {"family": "Fazel", "given": "S", "initials": "S"}, {"family": "D'Onofrio", "given": "B M", "initials": "BM"}, {"family": "L\u00e5ngstr\u00f6m", "given": "N", "initials": "N"}, {"family": "Larsson", "given": "H", "initials": "H"}, {"family": "Bergen", "given": "S E", "initials": "SE"}, {"family": "Kuja-Halkola", "given": "R", "initials": "R"}, {"family": "Lichtenstein", "given": "P", "initials": "P"}], "type": "journal article", "published": "2016-05-03", "journal": {"volume": "6", "issn": "2158-3188", "issue": null, "pages": "e796", "title": "Transl Psychiatry", "issn-l": "2158-3188"}, "abstract": "Neighborhood influences in the etiology of schizophrenia have been emphasized in a number of systematic reviews, but causality remains uncertain. To test the social drift hypothesis, we used three complementary genetically informed Swedish cohorts. First, we used nationwide Swedish data on approximately 760 000 full- and half-sibling pairs born between 1951 and 1974 and quantitative genetic models to study genetic and environmental influences on the overlap between schizophrenia in young adulthood and subsequent residence in socioeconomically deprived neighborhoods. Schizophrenia diagnoses were ascertained using the National Patient Registry. Second, we tested the overlap between childhood psychotic experiences and neighborhood deprivation in early adulthood in the longitudinal Twin Study of Child and Adolescent Development (TCHAD; n=2960). Third, we investigated to what extent polygenic risk scores for schizophrenia predicted residence in deprived neighborhoods during late adulthood using the TwinGene sample (n=6796). Sibling data suggested that living in deprived neighborhoods was substantially heritable; 65% (95% confidence interval (95% CI): 60-71%) of the variance was attributed to genetic influences. Although the correlation between schizophrenia and neighborhood deprivation was moderate in magnitude (r=0.22; 95% CI: 0.20-0.24), it was entirely explained by genetic influences. We replicated these findings in the TCHAD sample. Moreover, the association between polygenic risk for schizophrenia and neighborhood deprivation was statistically significant (R(2)=0.15%, P=0.002). Our findings are primarily consistent with a genetic selection interpretation where genetic liability for schizophrenia also predicts subsequent residence in socioeconomically deprived neighborhoods. Previous studies may have overemphasized the relative importance of environmental influences in the social drift of schizophrenia patients. Clinical and policy interventions will therefore benefit from the future identification of potentially causal pathways between different dimensions of cognitive functions and socioeconomic trajectories derived from studies adopting family-based research designs.", "doi": "10.1038/tp.2016.62", "pmid": "27138795", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "tp201662"}, {"db": "pmc", "key": "PMC5070045"}], "notes": [], "created": "2017-05-03T13:01:41.870Z", "modified": "2020-01-21T13:56:04.594Z"}, {"entity": "publication", "iuid": "ec90e115ccd04a53be01f112704a09a8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ec90e115ccd04a53be01f112704a09a8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ec90e115ccd04a53be01f112704a09a8"}}, "title": "Common SNPs explain some of the variation in the personality dimensions of neuroticism and extraversion.", "authors": [{"family": "Vinkhuyzen", "given": "A A E", "initials": "AA"}, {"family": "Pedersen", "given": "N L", "initials": "NL"}, {"family": "Yang", "given": "J", "initials": "J"}, {"family": "Lee", "given": "S H", "initials": "SH"}, {"family": "Magnusson", "given": "P K E", "initials": "PK"}, {"family": "Iacono", "given": "W G", "initials": "WG"}, {"family": "McGue", "given": "M", "initials": "M"}, {"family": "Madden", "given": "P A F", "initials": "PA"}, {"family": "Heath", "given": "A C", "initials": "AC"}, {"family": "Luciano", "given": "M", "initials": "M"}, {"family": "Payton", "given": "A", "initials": "A"}, {"family": "Horan", "given": "M", "initials": "M"}, {"family": "Ollier", "given": "W", "initials": "W"}, {"family": "Pendleton", "given": "N", "initials": "N"}, {"family": "Deary", "given": "I J", "initials": "IJ"}, {"family": "Montgomery", "given": "G W", "initials": "GW"}, {"family": "Martin", "given": "N G", "initials": "NG"}, {"family": "Visscher", "given": "P M", "initials": "PM"}, {"family": "Wray", "given": "N R", "initials": "NR"}], "type": "journal article", "published": "2012-04-17", "journal": {"volume": "2", "issn": "2158-3188", "issue": null, "pages": "e102", "title": "Transl Psychiatry", "issn-l": "2158-3188"}, "abstract": "The personality traits of neuroticism and extraversion are predictive of a number of social and behavioural outcomes and psychiatric disorders. Twin and family studies have reported moderate heritability estimates for both traits. Few associations have been reported between genetic variants and neuroticism/extraversion, but hardly any have been replicated. Moreover, the ones that have been replicated explain only a small proportion of the heritability (<~2%). Using genome-wide single-nucleotide polymorphism (SNP) data from ~12,000 unrelated individuals we estimated the proportion of phenotypic variance explained by variants in linkage disequilibrium with common SNPs as 0.06 (s.e. = 0.03) for neuroticism and 0.12 (s.e. = 0.03) for extraversion. In an additional series of analyses in a family-based sample, we show that while for both traits ~45% of the phenotypic variance can be explained by pedigree data (that is, expected genetic similarity) one third of this can be explained by SNP data (that is, realized genetic similarity). A part of the so-called 'missing heritability' has now been accounted for, but some of the reported heritability is still unexplained. Possible explanations for the remaining missing heritability are that: (i) rare variants that are not captured by common SNPs on current genotype platforms make a major contribution; and/ or (ii) the estimates of narrow sense heritability from twin and family studies are biased upwards, for example, by not properly accounting for nonadditive genetic factors and/or (common) environmental factors.", "doi": "10.1038/tp.2012.27", "pmid": "22832902", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "tp201227"}, {"db": "pmc", "key": "PMC3337075"}], "notes": [], "created": "2017-10-30T13:48:14.902Z", "modified": "2020-01-21T13:56:08.419Z"}], "created": "2017-05-09T09:12:30.125Z", "modified": "2020-11-27T13:14:09.289Z"}