{"entity": "researcher", "timestamp": "2026-08-11T08:13:25.598Z", "family": "H\u00e4gg", "given": "Sara", "initials": "S", "orcid": "0000-0002-2452-1500", "affiliations": ["Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/e1d010dfe5d84a33b6a6c7ec815ca3dc.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/e1d010dfe5d84a33b6a6c7ec815ca3dc"}}, "publications": [{"entity": "publication", "iuid": "919cf2bb62074bd48782a3c7c7263536", "links": {"self": {"href": "https://publications.scilifelab.se/publication/919cf2bb62074bd48782a3c7c7263536.json"}, "display": {"href": "https://publications.scilifelab.se/publication/919cf2bb62074bd48782a3c7c7263536"}}, "title": "Large-scale genome-wide analyses with proteomics integration reveal novel loci and biological insights into frailty.", "authors": [{"family": "Mak", "given": "Jonathan K L", "initials": "JKL", "orcid": "0000-0003-4454-8580", "researcher": {"href": "https://publications.scilifelab.se/researcher/4994e82ef4784f06aff8017a9cf9ad1c.json"}}, {"family": "Qin", "given": "Chenxi", "initials": "C"}, {"family": "Kr\u00fcger", "given": "Moritz", "initials": "M", "orcid": "0009-0005-7754-1950", "researcher": {"href": "https://publications.scilifelab.se/researcher/868a1b17a99c4fa1ac629e65f0dd636f.json"}}, {"family": "Kuukka", "given": "Anna", "initials": "A"}, {"family": "FinnGen", "given": "", "initials": ""}, {"family": "H\u00e4gg", "given": "Sara", "initials": "S", "orcid": "0000-0002-2452-1500", "researcher": {"href": "https://publications.scilifelab.se/researcher/e1d010dfe5d84a33b6a6c7ec815ca3dc.json"}}, {"family": "Lin", "given": "Jake", "initials": "J"}, {"family": "Jylh\u00e4v\u00e4", "given": "Juulia", "initials": "J", "orcid": "0000-0003-0250-4491", "researcher": {"href": "https://publications.scilifelab.se/researcher/5193964678264255adaaf5005ab59a87.json"}}], "type": "journal article", "published": "2025-08-00", "journal": {"title": "Nat Aging", "issn": "2662-8465", "volume": "5", "issue": "8", "pages": "1589-1600", "issn-l": null}, "abstract": "Frailty is a clinically relevant phenotype with notable gaps in our understanding of its etiology. Using the Hospital Frailty Risk Score (HFRS) to define frailty, we performed a genome-wide association study in FinnGen (N = 500,737), replicated the results in the UK Biobank (N = 407,463) and performed a meta-analysis. We prioritized genes through colocalization with expression, splicing and protein quantitative trait loci and proteomics integration. We identified 53 independent lead variants associated with frailty (P < 5 \u00d7 10-8), of which 45 were novel and not previously reported in the GWAS Catalog. Replication at the individual variant and polygenic risk score of the HFRS (P = 1.86 \u00d7 10-522) levels and meta-analysis largely confirmed the findings. Colocalization analysis supported a causal role for several genes, including CHST9, C6orf106 (ILRUN), KHK, MET, APOE, CGREF1 and PPP6C. Additionally, plasma levels of MET, CGREF1 and APOE were associated with HFRS. Our results reveal new genetic contributions to frailty and shed light on its biological basis.", "doi": "10.1038/s43587-025-00925-y", "pmid": "40764432", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12350161"}, {"db": "pii", "key": "10.1038/s43587-025-00925-y"}], "notes": [], "created": "2025-11-28T10:47:40.805Z", "modified": "2025-11-28T10:47:41.026Z"}, {"entity": "publication", "iuid": "39a3713a7f8e4699b510aad93490c0b4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/39a3713a7f8e4699b510aad93490c0b4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/39a3713a7f8e4699b510aad93490c0b4"}}, "title": "Associations between epigenetic aging and diabetes mellitus in a Swedish longitudinal study.", "authors": [{"family": "Wikstr\u00f6m Shemer", "given": "Daniel", "initials": "D"}, {"family": "Mostafaei", "given": "Shayan", "initials": "S"}, {"family": "Tang", "given": "Bowen", "initials": "B"}, {"family": "Pedersen", "given": "Nancy L", "initials": "NL"}, {"family": "Karlsson", "given": "Ida K", "initials": "IK"}, {"family": "Fall", "given": "Tove", "initials": "T"}, {"family": "H\u00e4gg", "given": "Sara", "initials": "S", "orcid": "0000-0002-2452-1500", "researcher": {"href": "https://publications.scilifelab.se/researcher/e1d010dfe5d84a33b6a6c7ec815ca3dc.json"}}], "type": "journal article", "published": "2024-10-00", "journal": {"title": "Geroscience", "issn": "2509-2723", "volume": "46", "issue": "5", "pages": "5003-5014", "issn-l": null}, "abstract": "Diabetes mellitus type 2 (T2D) is associated with accelerated biological aging and the increased risk of onset of other age-related diseases. Epigenetic changes in DNA methylation levels have been found to serve as reliable biomarkers for biological aging. This study explores the relationship between various epigenetic biomarkers of aging and diabetes risk using longitudinal data. Data from the Swedish Adoption/Twin Study of Aging (SATSA) was collected from 1984 to 2014 and included 536 individuals with at least one epigenetic measurement. The following epigenetic biomarkers of aging were employed: DNAm PAI-1, DNAmTL, DunedinPACE, PCHorvath1, PCHorvath2, PCHannum, PCPhenoAge, and PCGrimAge. Firstly, longitudinal analysis of biomarker trajectories was done. Secondly, linear correlations between the biomarkers and time to diabetes were studied within individuals developing diabetes. Thirdly, Cox proportional hazards (PH) models were used to assess the associations between these biomarkers and time of diabetes diagnosis, with adjustments for chronological age, sex, education, smoking, blood glucose, and BMI. The longitudinal trajectories of the biomarkers revealed differences between individuals with and without diabetes. Smoothened average curves for DunedinPACE and DNAm PAI-1 were higher for individuals with diabetes around the age 60-70, compared to controls. Likewise, DunedinPACE and DNAm PAI-1 were higher closer to diabetes onset. However, no significant associations were found between the epigenetic biomarkers of aging and risk of diabetes in Cox PH models. Our findings suggest the potential value of developing epigenetic biomarkers specifically tailored to T2D, should we wish to model and explore the potential for predicting the disease.", "doi": "10.1007/s11357-024-01252-7", "pmid": "38937415", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "NGI SNP genotyping": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11335983"}, {"db": "pii", "key": "10.1007/s11357-024-01252-7"}], "notes": [], "created": "2024-10-21T11:23:00.308Z", "modified": "2024-10-21T11:23:00.355Z"}, {"entity": "publication", "iuid": "7e532fb85545426880d8fb6fec942f51", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7e532fb85545426880d8fb6fec942f51.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7e532fb85545426880d8fb6fec942f51"}}, "title": "Epigenome-wide analysis of frailty: Results from two European twin cohorts.", "authors": [{"family": "Mak", "given": "Jonathan K L", "initials": "JKL", "orcid": "0000-0003-4454-8580", "researcher": {"href": "https://publications.scilifelab.se/researcher/4994e82ef4784f06aff8017a9cf9ad1c.json"}}, {"family": "Skovgaard", "given": "Asmus Cosmos", "initials": "AC"}, {"family": "Nygaard", "given": "Marianne", "initials": "M"}, {"family": "Kananen", "given": "Laura", "initials": "L", "orcid": "0000-0003-3742-8927", "researcher": {"href": "https://publications.scilifelab.se/researcher/b95c9eeb27214482bbbca978d69d79c7.json"}}, {"family": "Reynolds", "given": "Chandra A", "initials": "CA"}, {"family": "Wang", "given": "Yunzhang", "initials": "Y"}, {"family": "Kuja-Halkola", "given": "Ralf", "initials": "R"}, {"family": "Karlsson", "given": "Ida K", "initials": "IK", "orcid": "0000-0003-3605-7829", "researcher": {"href": "https://publications.scilifelab.se/researcher/b2c87ada82ae43df9753a891305ddb40.json"}}, {"family": "Pedersen", "given": "Nancy L", "initials": "NL"}, {"family": "H\u00e4gg", "given": "Sara", "initials": "S", "orcid": "0000-0002-2452-1500", "researcher": {"href": "https://publications.scilifelab.se/researcher/e1d010dfe5d84a33b6a6c7ec815ca3dc.json"}}, {"family": "Soerensen", "given": "Mette", "initials": "M"}, {"family": "Jylh\u00e4v\u00e4", "given": "Juulia", "initials": "J"}], "type": "journal article", "published": "2024-02-27", "journal": {"title": "Aging Cell", "issn": "1474-9726", "pages": "e14135", "issn-l": "1474-9718"}, "abstract": "Epigenetics plays an important role in the aging process, but it is unclear whether epigenetic factors also influence frailty, an age-related state of physiological decline. In this study, we performed a meta-analysis of epigenome-wide association studies in four samples drawn from the Swedish Adoption/Twin Study of Aging (SATSA) and the Longitudinal Study of Aging Danish Twins (LSADT) to explore the association between DNA methylation and frailty. Frailty was defined using the frailty index (FI), and DNA methylation levels were measured in whole blood using Illumina's Infinium HumanMethylation450K and MethylationEPIC arrays. In the meta-analysis consisting of a total of 829 participants, we identified 589 CpG sites that were statistically significantly associated with either the continuous or categorical FI (false discovery rate <0.05). Many of these CpGs have previously been associated with age and age-related diseases. The identified sites were also largely directionally consistent in a longitudinal analysis using mixed-effects models in SATSA, where the participants were followed up to a maximum of 20 years. Moreover, we identified three differentially methylated regions within the MGRN1, MIR596, and TAPBP genes that have been linked to neuronal aging, tumor growth, and immune functions. Furthermore, our meta-analysis results replicated 34 of the 77 previously reported frailty-associated CpGs at p < 0.05. In conclusion, our findings demonstrate robust associations between frailty and DNA methylation levels in 589 novel CpGs, previously unidentified for frailty, and strengthen the role of neuronal/brain pathways in frailty.", "doi": "10.1111/acel.14135", "pmid": "38414347", "labels": {"NGI Short read": "Service", "NGI SNP genotyping": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [], "notes": [], "created": "2024-03-21T08:58:19.904Z", "modified": "2024-03-21T08:58:20.068Z"}, {"entity": "publication", "iuid": "b7ade62398f54e0284d41dfed05b1a6e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b7ade62398f54e0284d41dfed05b1a6e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b7ade62398f54e0284d41dfed05b1a6e"}}, "title": "Longitudinal associations between use of antihypertensive, antidiabetic, and lipid-lowering medications and biological aging.", "authors": [{"family": "Tang", "given": "Bowen", "initials": "B"}, {"family": "Li", "given": "Xia", "initials": "X"}, {"family": "Wang", "given": "Yunzhang", "initials": "Y"}, {"family": "Sj\u00f6lander", "given": "Arvid", "initials": "A"}, {"family": "Johnell", "given": "Kristina", "initials": "K"}, {"family": "Thambisetty", "given": "Madhav", "initials": "M"}, {"family": "Ferrucci", "given": "Luigi", "initials": "L"}, {"family": "Reynolds", "given": "Chandra A", "initials": "CA"}, {"family": "Finkel", "given": "Deborah", "initials": "D"}, {"family": "Jylh\u00e4v\u00e4", "given": "Juulia", "initials": "J"}, {"family": "Pedersen", "given": "Nancy L", "initials": "NL"}, {"family": "H\u00e4gg", "given": "Sara", "initials": "S", "orcid": "0000-0002-2452-1500", "researcher": {"href": "https://publications.scilifelab.se/researcher/e1d010dfe5d84a33b6a6c7ec815ca3dc.json"}}], "type": "journal article", "published": "2023-04-10", "journal": {"title": "Geroscience", "issn": "2509-2723", "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": "Aging is a major risk factor for many chronic diseases. This study aimed to examine the effects of antihypertensive, lipid-lowering, and antidiabetic drugs on biological aging. We included 672 participants and 2746 repeated measurements from the Swedish Adoption/Twin Study of Aging. Self-reported medicine uses were categorized into antidiabetic, antihypertensive, and lipid-lowering drugs. A total of 12 biomarkers for biological aging (BA biomarkers) were included as outcomes. Conditional generalized estimating equations were applied conditioning on individuals to estimate the drug effect on BA biomarker level within the same person when using or not using the drug. Chronological age, body mass index, smoking status, number of multiple medication uses, blood pressure, blood glucose level, and apoB/apoA ratio were adjusted for as covariates in the model. Overall, using antihypertensive drugs was associated with a decrease in one DNA-methylation age (PCGrimAge: beta = - 0.39, 95%CI = - 0.67 to - 0.12). When looking into drug subcategories, calcium channel blockers (CCBs) were associated with a decrease in several DNA-methylation ages (PCHorvathAge beta = - 1.28, 95%CI = - 2.34 to - 0.21; PCSkin&bloodAge beta = - 1.34, 95%CI = - 2.61 to - 0.07; PCPhenoAge beta = - 1.74, 95%CI = - 2.58 to - 0.89; PCGrimAge beta = - 0.57, 95%CI = - 0.96 to - 0.17) and in functional biological ages (functional age index beta = - 2.18, 95%CI = - 3.65 to - 0.71; frailty index beta = - 1.31, 95%CI = - 2.43 to - 0.18). However, the results within other drug subcategories were inconsistent. Calcium channel blockers may decrease biological aging captured by the BA biomarkers measured at epigenetic and functional level. Future studies are warranted to confirm these effects and understand the underlying biological mechanisms.", "doi": "10.1007/s11357-023-00784-8", "pmid": "37032369", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "NGI SNP genotyping": "Service"}, "xrefs": [{"db": "pii", "key": "10.1007/s11357-023-00784-8"}], "notes": [], "created": "2023-05-15T11:41:57.546Z", "modified": "2023-06-02T15:25:45.521Z"}, {"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": "c0b22b8488e949e984ce8d0398e5ef9b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c0b22b8488e949e984ce8d0398e5ef9b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c0b22b8488e949e984ce8d0398e5ef9b"}}, "title": "A genome-wide association study of the frailty index highlights brain pathways in ageing.", "authors": [{"family": "Atkins", "given": "Janice L", "initials": "JL", "orcid": "0000-0003-4919-9068", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d251cfaba844c7d866ad2cd624e25ce.json"}}, {"family": "Jylh\u00e4v\u00e4", "given": "Juulia", "initials": "J"}, {"family": "Pedersen", "given": "Nancy L", "initials": "NL"}, {"family": "Magnusson", "given": "Patrik K", "initials": "PK"}, {"family": "Lu", "given": "Yi", "initials": "Y"}, {"family": "Wang", "given": "Yunzhang", "initials": "Y"}, {"family": "H\u00e4gg", "given": "Sara", "initials": "S", "orcid": "0000-0002-2452-1500", "researcher": {"href": "https://publications.scilifelab.se/researcher/e1d010dfe5d84a33b6a6c7ec815ca3dc.json"}}, {"family": "Melzer", "given": "David", "initials": "D"}, {"family": "Williams", "given": "Dylan M", "initials": "DM"}, {"family": "Pilling", "given": "Luke C", "initials": "LC", "orcid": "0000-0002-3332-8454", "researcher": {"href": "https://publications.scilifelab.se/researcher/aadea4e5796940d88b315b83530162e4.json"}}], "type": "journal article", "published": "2021-09-00", "journal": {"title": "Aging Cell", "issn": "1474-9726", "issn-l": "1474-9718", "volume": "20", "issue": "9", "pages": "e13459"}, "abstract": "Frailty is a common geriatric syndrome and strongly associated with disability, mortality and hospitalization. Frailty is commonly measured using the frailty index (FI), based on the accumulation of a number of health deficits during the life course. The mechanisms underlying FI are multifactorial and not well understood, but a genetic basis has been suggested with heritability estimates between 30 and 45%. Understanding the genetic determinants and biological mechanisms underpinning FI may help to delay or even prevent frailty. We performed a genome-wide association study (GWAS) meta-analysis of a frailty index in European descent UK Biobank participants (n = 164,610, 60-70 years) and Swedish TwinGene participants (n = 10,616, 41-87 years). FI calculation was based on 49 or 44 self-reported items on symptoms, disabilities and diagnosed diseases for UK Biobank and TwinGene, respectively. 14 loci were associated with the FI (p < 5*10-8 ). Many FI-associated loci have established associations with traits such as body mass index, cardiovascular disease, smoking, HLA proteins, depression and neuroticism; however, one appears to be novel. The estimated single nucleotide polymorphism (SNP) heritability of the FI was 11% (0.11, SE 0.005). In enrichment analysis, genes expressed in the frontal cortex and hippocampus were significantly downregulated (adjusted p < 0.05). We also used Mendelian randomization to identify modifiable traits and exposures that may affect frailty risk, with a higher educational attainment genetic risk score being associated with a lower degree of frailty. Risk of frailty is influenced by many genetic factors, including well-known disease risk factors and mental health, with particular emphasis on pathways in the brain.", "doi": "10.1111/acel.13459", "pmid": "34431594", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8441299"}], "notes": [], "created": "2021-09-07T11:11:44.764Z", "modified": "2021-12-07T07:30:15.087Z"}, {"entity": "publication", "iuid": "b70be864396f40b68d30939cc4e01962", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b70be864396f40b68d30939cc4e01962.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b70be864396f40b68d30939cc4e01962"}}, "title": "Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.", "authors": [{"family": "de Rojas", "given": "Itziar", "initials": "I", "orcid": "0000-0002-2148-381X", "researcher": {"href": 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"https://publications.scilifelab.se/researcher/5e646be026ce42ecbfd4d62eca3f9bce.json"}}, {"family": "Huisman", "given": "Martijn", "initials": "M"}, {"family": "Andreassen", "given": "Ole A", "initials": "OA", "orcid": "0000-0002-4461-3568", "researcher": {"href": "https://publications.scilifelab.se/researcher/56f384e8e2fd4a7383c7b26e88a828b2.json"}}, {"family": "Posthuma", "given": "Danielle", "initials": "D"}, {"family": "Clarim\u00f3n", "given": "Jordi", "initials": "J"}, {"family": "Boada", "given": "Merc\u00e8", "initials": "M", "orcid": "0000-0003-2617-3009", "researcher": {"href": "https://publications.scilifelab.se/researcher/c8d00c33569e41b481cf5cdc99cd96e9.json"}}, {"family": "van der Flier", "given": "Wiesje M", "initials": "WM", "orcid": "0000-0001-8766-6224", "researcher": {"href": "https://publications.scilifelab.se/researcher/0b32776a9e524f299765506b6dbe9768.json"}}, {"family": "Ramirez", "given": "Alfredo", "initials": "A", "orcid": "0000-0003-4991-763X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a8995a57e82f4f479ab8251175aeb8d6.json"}}, {"family": "Lambert", "given": "Jean-Charles", "initials": "JC", "orcid": "0000-0003-0829-7817", "researcher": {"href": "https://publications.scilifelab.se/researcher/a0ec452344144906b7e8be95eb8c62d6.json"}}, {"family": "van der Lee", "given": "Sven J", "initials": "SJ", "orcid": "0000-0003-1606-8643", "researcher": {"href": "https://publications.scilifelab.se/researcher/9a34a1b7b98b4360b48dafe3f0d5dcb2.json"}}, {"family": "Ruiz", "given": "Agust\u00edn", "initials": "A", "orcid": "0000-0003-2633-2495", "researcher": {"href": "https://publications.scilifelab.se/researcher/33a263bd6bd24ca897c988d4fcbcaca1.json"}}], "type": "journal article", "published": "2021-06-07", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "12", "issue": "1", "pages": "3417"}, "abstract": "Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE \u025b4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease.", "doi": "10.1038/s41467-021-22491-8", "pmid": "34099642", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8184987"}, {"db": "pii", "key": "10.1038/s41467-021-22491-8"}], "notes": [], "created": "2021-08-19T13:41:32.762Z", "modified": "2023-06-20T15:56:47.699Z"}, {"entity": "publication", "iuid": "3781a12ed3544fa9b3e1a2daa02dc54b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3781a12ed3544fa9b3e1a2daa02dc54b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3781a12ed3544fa9b3e1a2daa02dc54b"}}, "title": "DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan.", "authors": [{"family": "van Dongen", "given": "Jenny", "initials": "J", "orcid": "0000-0003-2063-8741", "researcher": {"href": "https://publications.scilifelab.se/researcher/fc28125d1b68438ea1a419437ad335c9.json"}}, {"family": "Hagenbeek", "given": "Fiona A", "initials": "FA", "orcid": "0000-0002-8773-0430", "researcher": {"href": "https://publications.scilifelab.se/researcher/1874bbcb93ed4633879199558ae54877.json"}}, {"family": "Suderman", "given": "Matthew", "initials": "M"}, {"family": "Roetman", "given": "Peter J", "initials": "PJ", "orcid": "0000-0002-6495-962X", "researcher": {"href": "https://publications.scilifelab.se/researcher/bd0b47e8144d4b0ab0c3bad505a1636f.json"}}, {"family": "Sugden", "given": "Karen", "initials": "K"}, {"family": "Chiocchetti", "given": "Andreas G", "initials": "AG", "orcid": "0000-0002-7329-9985", "researcher": {"href": "https://publications.scilifelab.se/researcher/b90b3aecf61a44f090e0511a52b0ebec.json"}}, {"family": "Ismail", "given": 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"researcher": {"href": "https://publications.scilifelab.se/researcher/b3e25818ffe646f8a843b8fea4fa1eee.json"}}, {"family": "Send", "given": "Tabea S", "initials": "TS"}, {"family": "Frank", "given": "Josef", "initials": "J", "orcid": "0000-0003-4867-9465", "researcher": {"href": "https://publications.scilifelab.se/researcher/041d6a59ba7d4c2dab9706861964bce1.json"}}, {"family": "Jylh\u00e4v\u00e4", "given": "Juulia", "initials": "J"}, {"family": "Wang", "given": "Yunzhang", "initials": "Y"}, {"family": "Mishra", "given": "Pashupati Prasad", "initials": "PP"}, {"family": "Colins", "given": "Olivier F", "initials": "OF", "orcid": "0000-0001-9532-2544", "researcher": {"href": "https://publications.scilifelab.se/researcher/ec63c561cea24f0bb78e8b92c6c5a82d.json"}}, {"family": "Corcoran", "given": "David L", "initials": "DL", "orcid": "0000-0001-7460-9247", "researcher": {"href": "https://publications.scilifelab.se/researcher/30eb6bb04e7846b58c7fa33a75cf3a51.json"}}, {"family": "Poulton", "given": "Richie", "initials": "R", "orcid": "0000-0002-1052-4583", "researcher": {"href": "https://publications.scilifelab.se/researcher/8f61fd90a9804126b169485da8cf65a1.json"}}, {"family": "Mill", "given": "Jonathan", "initials": "J", "orcid": "0000-0003-1115-3224", "researcher": {"href": "https://publications.scilifelab.se/researcher/480aff443bbd4605b3dd65736c08932e.json"}}, {"family": "Hannon", "given": "Eilis", "initials": "E", "orcid": "0000-0001-6840-072X", "researcher": {"href": "https://publications.scilifelab.se/researcher/2e059e0c152744da96bbfa7a26b4741f.json"}}, {"family": "Arseneault", "given": "Louise", "initials": "L", "orcid": "0000-0002-2938-2191", "researcher": {"href": "https://publications.scilifelab.se/researcher/0664e4afe7de4354924a1b39b87cf570.json"}}, {"family": "Korhonen", "given": "Tellervo", "initials": "T"}, {"family": "Vuoksimaa", "given": "Eero", "initials": "E"}, {"family": "Felix", "given": "Janine F", "initials": "JF", "orcid": "0000-0002-9801-5774", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a4482378cb24a9f832729f7004a41bf.json"}}, {"family": "Bakermans-Kranenburg", "given": "Marian J", "initials": "MJ", "orcid": "0000-0001-7763-0711", "researcher": {"href": "https://publications.scilifelab.se/researcher/11233b4bc1be47ca8248ac062f859e81.json"}}, {"family": "Campbell", "given": "Archie", "initials": "A", "orcid": "0000-0003-0198-5078", "researcher": {"href": "https://publications.scilifelab.se/researcher/89d6b9cb975246e5aa97c60035e2fdcc.json"}}, {"family": "Czamara", "given": "Darina", "initials": "D", "orcid": "0000-0001-7381-904X", "researcher": {"href": "https://publications.scilifelab.se/researcher/0e9a8a7d605d4f63a311fc8a211422a6.json"}}, {"family": "Binder", "given": "Elisabeth", "initials": "E", "orcid": "0000-0001-7088-6618", "researcher": {"href": "https://publications.scilifelab.se/researcher/0cfb2bf09e9d49ad922bb5c3c252c716.json"}}, {"family": "Corpeleijn", "given": "Eva", "initials": "E"}, {"family": "Gonzalez", "given": "Juan R", "initials": "JR", "orcid": "0000-0003-3267-2146", "researcher": {"href": "https://publications.scilifelab.se/researcher/0898265a25ee4d14b875e14d7ff09479.json"}}, {"family": "Grazuleviciene", "given": "Regina", "initials": "R", "orcid": "0000-0002-0210-8053", "researcher": {"href": "https://publications.scilifelab.se/researcher/223bfb218f2e49bf999bd1521369ba83.json"}}, {"family": "Gutzkow", "given": "Kristine B", "initials": "KB"}, {"family": "Evandt", "given": "Jorunn", "initials": "J"}, {"family": "Vafeiadi", "given": "Marina", "initials": "M", "orcid": "0000-0002-6143-7172", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb8527777ad8409c89344e0b455365e7.json"}}, {"family": "Klein", "given": "Marieke", "initials": "M", "orcid": "0000-0001-8784-5679", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7481a7b70b6411b98c77e27e0de9b2f.json"}}, {"family": "van der Meer", "given": "Dennis", "initials": "D", "orcid": "0000-0002-0466-386X", "researcher": {"href": "https://publications.scilifelab.se/researcher/77320b76a77b4045af6228ee5258f41e.json"}}, {"family": "Ligthart", "given": "Lannie", "initials": "L", "orcid": "0000-0002-6570-3319", "researcher": {"href": "https://publications.scilifelab.se/researcher/c352ff3a891d4eb5bfe9c0260238ef79.json"}}, {"family": "BIOS Consortium", "given": "", "initials": ""}, {"family": "Kluft", "given": "Cornelis", "initials": "C"}, {"family": "Davies", "given": "Gareth E", "initials": "GE"}, {"family": "Hakulinen", "given": "Christian", "initials": "C"}, {"family": "Keltikangas-J\u00e4rvinen", "given": "Liisa", "initials": "L"}, {"family": "Franke", "given": "Barbara", "initials": "B", "orcid": "0000-0003-4375-6572", "researcher": {"href": "https://publications.scilifelab.se/researcher/105f0131cfc34a668ed840e622e4f902.json"}}, {"family": "Freitag", "given": "Christine M", "initials": "CM", "orcid": "0000-0001-9676-4782", "researcher": {"href": "https://publications.scilifelab.se/researcher/5d9f9f97c28b4919b09be5c1292a806b.json"}}, {"family": "Konrad", "given": "Kerstin", "initials": "K", "orcid": "0000-0001-9039-2615", "researcher": {"href": "https://publications.scilifelab.se/researcher/4b063642dc3d425a8037e2cc0ff3a067.json"}}, {"family": "Hervas", "given": "Amaia", "initials": "A"}, {"family": "Fern\u00e1ndez-Rivas", "given": "Aranzazu", "initials": "A"}, {"family": "Vetro", "given": "Agnes", "initials": "A"}, {"family": "Raitakari", "given": "Olli", "initials": "O"}, {"family": "Lehtim\u00e4ki", "given": "Terho", "initials": "T", "orcid": "0000-0002-2555-4427", "researcher": {"href": "https://publications.scilifelab.se/researcher/03ed59707dae4c8fb9e63ac1f7c398e3.json"}}, {"family": "Vermeiren", "given": "Robert", "initials": "R"}, {"family": "Strandberg", "given": "Timo", "initials": "T"}, {"family": "R\u00e4ikk\u00f6nen", "given": "Katri", "initials": "K"}, {"family": "Snieder", "given": "Harold", "initials": "H", "orcid": "0000-0003-1949-2298", "researcher": {"href": "https://publications.scilifelab.se/researcher/e9276827839a4f3cb50dcaa2ad4708a5.json"}}, {"family": "Witt", "given": "Stephanie H", "initials": "SH", "orcid": "0000-0002-1571-1468", "researcher": {"href": "https://publications.scilifelab.se/researcher/88c8da59196f4adb8a57509e5e9e85ef.json"}}, {"family": "Deuschle", "given": "Michael", "initials": "M"}, {"family": "Pedersen", "given": "Nancy L", "initials": "NL"}, {"family": "H\u00e4gg", "given": "Sara", "initials": "S", "orcid": "0000-0002-2452-1500", "researcher": {"href": "https://publications.scilifelab.se/researcher/e1d010dfe5d84a33b6a6c7ec815ca3dc.json"}}, {"family": "Sunyer", "given": "Jordi", "initials": "J"}, {"family": "Franke", "given": "Lude", "initials": "L"}, {"family": "Kaprio", "given": "Jaakko", "initials": "J", "orcid": "0000-0002-3716-2455", "researcher": {"href": "https://publications.scilifelab.se/researcher/814d362333844b72a70cba9ebcf61e6f.json"}}, {"family": "Ollikainen", "given": "Miina", "initials": "M", "orcid": "0000-0003-3661-7400", "researcher": {"href": "https://publications.scilifelab.se/researcher/0cda8a90eedd4d179a230bc5377d3989.json"}}, {"family": "Moffitt", "given": "Terrie E", "initials": "TE"}, {"family": "Tiemeier", "given": "Henning", "initials": "H", "orcid": "0000-0002-4395-1397", "researcher": {"href": "https://publications.scilifelab.se/researcher/73e05bd74af344ba8d963463f49bb242.json"}}, {"family": "van IJzendoorn", "given": "Marinus H", "initials": "MH", "orcid": "0000-0003-1144-454X", "researcher": {"href": "https://publications.scilifelab.se/researcher/d8ae6deb331f4c52b835210f42c65abe.json"}}, {"family": "Relton", "given": "Caroline", "initials": "C"}, {"family": "Vrijheid", "given": "Martine", "initials": "M", "orcid": "0000-0002-7090-1758", "researcher": {"href": "https://publications.scilifelab.se/researcher/ccf0ebb5d1664b99bbb460c194d2f361.json"}}, {"family": "Sebert", "given": "Sylvain", "initials": "S", "orcid": "0000-0001-6681-6983", "researcher": {"href": "https://publications.scilifelab.se/researcher/c007e85f69d4421bb6cf76dc52a01eb8.json"}}, {"family": "Jarvelin", "given": "Marjo-Riitta", "initials": "M"}, {"family": "Caspi", "given": "Avshalom", "initials": "A"}, {"family": "Evans", "given": "Kathryn L", "initials": "KL", "orcid": "0000-0002-7884-5877", "researcher": {"href": "https://publications.scilifelab.se/researcher/2985078354be4ab19f96d66fa9b2c8cc.json"}}, {"family": "McIntosh", "given": "Andrew M", "initials": "AM", "orcid": "0000-0002-0198-4588", "researcher": {"href": "https://publications.scilifelab.se/researcher/cbac1cee97084746b97442ec39efe91b.json"}}, {"family": "Bartels", "given": "Meike", "initials": "M", "orcid": "0000-0002-9667-7555", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a91c095e993411b99e81e21f40d8597.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": "2021-06-00", "journal": {"title": "Mol. Psychiatry", "issn": "1476-5578", "issn-l": "1359-4184", "volume": "26", "issue": "6", "pages": "2148-2162"}, "abstract": "DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 \u00d7 10-7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3-82%) of the aggression-methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.", "doi": "10.1038/s41380-020-00987-x", "pmid": "33420481", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41380-020-00987-x"}, {"db": "pmc", "key": "PMC8263810"}, {"db": "mid", "key": "EMS114691"}], "notes": [], "created": "2021-01-14T11:58:55.708Z", "modified": "2021-12-07T13:43:00.672Z"}, {"entity": "publication", "iuid": "4a9b528a26aa47e38f232b961ded646c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4a9b528a26aa47e38f232b961ded646c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4a9b528a26aa47e38f232b961ded646c"}}, "title": "A decade of epigenetic change in aging twins: Genetic and environmental contributions to longitudinal DNA methylation.", "authors": [{"family": "Reynolds", "given": "Chandra A", "initials": "CA", "orcid": "0000-0001-6502-7173", "researcher": {"href": "https://publications.scilifelab.se/researcher/6b7cd2b82d81463c8dd3f13c4d75ab6f.json"}}, {"family": "Tan", "given": "Qihua", "initials": "Q"}, {"family": "Munoz", "given": "Elizabeth", "initials": "E"}, {"family": "Jylh\u00e4v\u00e4", "given": "Juulia", "initials": "J"}, {"family": "Hjelmborg", "given": "Jacob", "initials": "J"}, {"family": "Christiansen", "given": "Lene", "initials": "L"}, {"family": "H\u00e4gg", "given": "Sara", "initials": "S", "orcid": "0000-0002-2452-1500", "researcher": {"href": "https://publications.scilifelab.se/researcher/e1d010dfe5d84a33b6a6c7ec815ca3dc.json"}}, {"family": "Pedersen", "given": "Nancy L", "initials": "NL"}], "type": "journal article", "published": "2020-08-00", "journal": {"title": "Aging Cell", "issn": "1474-9726", "volume": "19", "issue": "8", "pages": "e13197", "issn-l": "1474-9718"}, "abstract": "Epigenetic changes may result from the interplay of environmental exposures and genetic influences and contribute to differences in age-related disease, disability, and mortality risk. However, the etiologies contributing to stability and change in DNA methylation have rarely been examined longitudinally.\n\nWe considered DNA methylation in whole blood leukocyte DNA across a 10-year span in two samples of same-sex aging twins: (a) Swedish Adoption Twin Study of Aging (SATSA; N = 53 pairs, 53% female; 62.9 and 72.5 years, SD = 7.2 years); (b) Longitudinal Study of Aging Danish Twins (LSADT; N = 43 pairs, 72% female, 76.2 and 86.1 years, SD=1.8 years). Joint biometrical analyses were conducted on 358,836 methylation probes in common. Bivariate twin models were fitted, adjusting for age, sex, and country.\n\nOverall, results suggest genetic contributions to DNA methylation across 358,836 sites tended to be small and lessen across 10 years (broad heritability M = 23.8% and 18.0%) but contributed to stability across time while person-specific factors explained emergent influences across the decade. Aging-specific sites identified from prior EWAS and methylation age clocks were more heritable than background sites. The 5037 sites that showed the greatest heritable/familial-environmental influences (p < 1E-07) were enriched for immune and inflammation pathways while 2020 low stability sites showed enrichment in stress-related pathways.\n\nAcross time, stability in methylation is primarily due to genetic contributions, while novel experiences and exposures contribute to methylation differences. Elevated genetic contributions at age-related methylation sites suggest that adaptions to aging and senescence may be differentially impacted by genetic background.", "doi": "10.1111/acel.13197", "pmid": "32710526", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7431820"}], "notes": [], "created": "2020-08-04T14:50:02.748Z", "modified": "2024-01-16T13:48:42.094Z"}, {"entity": "publication", "iuid": "7d10557c49554f21b70aaf8ab173723b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7d10557c49554f21b70aaf8ab173723b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7d10557c49554f21b70aaf8ab173723b"}}, "title": "Longitudinal trajectories, correlations and mortality associations of nine biological ages across 20-years follow-up.", "authors": [{"family": "Li", "given": "Xia", "initials": "X", "orcid": "0000-0003-1922-7152", "researcher": {"href": "https://publications.scilifelab.se/researcher/862fd8b41938458f9105c5bb73c35294.json"}}, {"family": "Ploner", "given": "Alexander", "initials": "A", "orcid": "0000-0002-5042-8326", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1b8cb5cffa4b69b057e2f94ac08d3b.json"}}, {"family": "Wang", "given": "Yunzhang", "initials": "Y"}, {"family": "Magnusson", "given": "Patrik Ke", "initials": "PK"}, {"family": "Reynolds", "given": "Chandra", "initials": "C"}, {"family": "Finkel", "given": "Deborah", "initials": "D"}, {"family": "Pedersen", "given": "Nancy L", "initials": "NL"}, {"family": "Jylh\u00e4v\u00e4", "given": "Juulia", "initials": "J"}, {"family": "H\u00e4gg", "given": "Sara", "initials": "S", "orcid": "0000-0002-2452-1500", "researcher": {"href": "https://publications.scilifelab.se/researcher/e1d010dfe5d84a33b6a6c7ec815ca3dc.json"}}], "type": "journal article", "published": "2020-02-11", "journal": {"title": "Elife", "issn": "2050-084X", "volume": "9", "issue": null, "issn-l": "2050-084X"}, "abstract": "Biological age measurements (BAs) assess aging-related physiological change and predict health risks among individuals of the same chronological age (CA). Multiple BAs have been proposed and are well studied individually but not jointly. We included 845 individuals and 3973 repeated measurements from a Swedish population-based cohort and examined longitudinal trajectories, correlations, and mortality associations of nine BAs across 20 years follow-up. We found the longitudinal growth of functional BAs accelerated around age 70; average levels of BA curves differed by sex across the age span (50-90 years). All BAs were correlated to varying degrees; correlations were mostly explained by CA. Individually, all BAs except for telomere length were associated with mortality risk independently of CA. The largest effects were seen for methylation age estimators (GrimAge) and the frailty index (FI). In joint models, two methylation age estimators (Horvath and GrimAge) and FI remained predictive, suggesting they are complementary in predicting mortality.", "doi": "10.7554/eLife.51507", "pmid": "32041686", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "51507"}, {"db": "pmc", "key": "PMC7012595"}], "notes": [], "created": "2020-02-27T09:21:02.553Z", "modified": "2024-01-16T13:48:42.960Z"}, {"entity": "publication", "iuid": "ad07a7341fca458f96005a035573c8ce", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ad07a7341fca458f96005a035573c8ce.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ad07a7341fca458f96005a035573c8ce"}}, "title": "Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk.", "authors": [{"family": "Jansen", "given": "Iris E", "initials": "IE", "orcid": "0000-0003-1901-8131", "researcher": {"href": "https://publications.scilifelab.se/researcher/0023d0046d8844abac6b071beabf71b8.json"}}, {"family": "Savage", "given": "Jeanne E", "initials": "JE", "orcid": "0000-0002-2034-8341", "researcher": {"href": "https://publications.scilifelab.se/researcher/d8768341f7f44f449c2f70a493cc556d.json"}}, {"family": "Watanabe", "given": "Kyoko", "initials": "K"}, {"family": "Bryois", "given": "Julien", "initials": "J"}, {"family": "Williams", "given": "Dylan M", "initials": "DM"}, {"family": "Steinberg", "given": "Stacy", "initials": "S", "orcid": "0000-0001-7726-5152", "researcher": {"href": "https://publications.scilifelab.se/researcher/9051c5beba2742ffabdd386bf9939fd3.json"}}, {"family": "Sealock", "given": "Julia", "initials": "J"}, {"family": "Karlsson", "given": "Ida K", "initials": "IK"}, {"family": "H\u00e4gg", "given": "Sara", "initials": "S", "orcid": "0000-0002-2452-1500", "researcher": {"href": "https://publications.scilifelab.se/researcher/e1d010dfe5d84a33b6a6c7ec815ca3dc.json"}}, {"family": "Athanasiu", "given": "Lavinia", "initials": "L"}, {"family": "Voyle", "given": "Nicola", "initials": "N"}, {"family": "Proitsi", "given": "Petroula", "initials": "P", "orcid": "0000-0002-2553-6974", "researcher": {"href": "https://publications.scilifelab.se/researcher/724f31ac8bc746e7801728be49ab9cc2.json"}}, {"family": "Witoelar", "given": "Aree", "initials": "A"}, {"family": "Stringer", "given": "Sven", "initials": "S", "orcid": "0000-0003-3115-8532", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7e6ae56d0474688b3722f58d33f385d.json"}}, {"family": "Aarsland", "given": "Dag", "initials": "D", "orcid": "0000-0001-6314-216X", "researcher": {"href": "https://publications.scilifelab.se/researcher/121af6702db54d68b1ca94e8c22a8688.json"}}, {"family": "Almdahl", "given": "Ina S", "initials": "IS", "orcid": "0000-0001-6070-4921", "researcher": {"href": "https://publications.scilifelab.se/researcher/8c99e3bce167471ba669e820cc6e0839.json"}}, {"family": "Andersen", "given": "Fred", "initials": "F"}, {"family": "Bergh", "given": "Sverre", "initials": "S"}, {"family": "Bettella", "given": "Francesco", "initials": "F"}, {"family": "Bjornsson", "given": "Sigurbjorn", "initials": "S"}, {"family": "Br\u00e6khus", "given": "Anne", "initials": "A"}, {"family": "Br\u00e5then", "given": "Geir", "initials": "G", "orcid": "0000-0003-3224-7983", "researcher": {"href": "https://publications.scilifelab.se/researcher/52e7ea4ab30548829139064396d7c044.json"}}, {"family": "de Leeuw", "given": "Christiaan", "initials": "C", "orcid": "0000-0003-1076-9828", "researcher": {"href": "https://publications.scilifelab.se/researcher/54a93840c735496c81a9514bbc564849.json"}}, {"family": "Desikan", "given": "Rahul S", "initials": "RS"}, {"family": "Djurovic", "given": "Srdjan", "initials": "S", "orcid": "0000-0002-8140-8061", "researcher": {"href": "https://publications.scilifelab.se/researcher/906538321c8e4f38b6bb4a7b0bc18fa3.json"}}, {"family": "Dumitrescu", "given": "Logan", "initials": "L"}, {"family": "Fladby", "given": "Tormod", "initials": "T"}, {"family": "Hohman", "given": "Timothy J", "initials": "TJ", "orcid": "0000-0002-3377-7014", "researcher": {"href": "https://publications.scilifelab.se/researcher/079a5de2cf894db3b46faa3f6ba1e04e.json"}}, {"family": "Jonsson", "given": "Palmi V", "initials": "PV"}, {"family": "Kiddle", "given": "Steven J", "initials": "SJ", "orcid": "0000-0003-4350-7437", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f86c2bca0014cf9aef8c215d97ce39c.json"}}, {"family": "Rongve", "given": "Arvid", "initials": "A"}, {"family": "Saltvedt", "given": "Ingvild", "initials": "I"}, {"family": "Sando", "given": "Sigrid B", "initials": "SB"}, {"family": "Selb\u00e6k", "given": "Geir", "initials": "G"}, {"family": "Shoai", "given": "Maryam", "initials": "M"}, {"family": "Skene", "given": "Nathan G", "initials": "NG", "orcid": "0000-0002-6807-3180", "researcher": {"href": "https://publications.scilifelab.se/researcher/0b4340cc0fa948eda26ce5618ebc0693.json"}}, {"family": "Snaedal", "given": "Jon", "initials": "J"}, {"family": "Stordal", "given": "Eystein", "initials": "E", "orcid": "0000-0002-2443-7923", "researcher": {"href": "https://publications.scilifelab.se/researcher/6eacc414991448c38cee92ac328eb4d3.json"}}, {"family": "Ulstein", "given": "Ingun D", "initials": "ID"}, {"family": "Wang", "given": "Yunpeng", "initials": "Y"}, {"family": "White", "given": "Linda R", "initials": "LR"}, {"family": "Hardy", "given": "John", "initials": "J"}, {"family": "Hjerling-Leffler", "given": "Jens", "initials": "J", "orcid": "0000-0002-4539-1776", "researcher": {"href": "https://publications.scilifelab.se/researcher/51675f0ff9aa47d89d6b2eb84a14820a.json"}}, {"family": "Sullivan", "given": "Patrick F", "initials": "PF"}, {"family": "van der Flier", "given": "Wiesje M", "initials": "WM"}, {"family": "Dobson", "given": "Richard", "initials": "R", "orcid": "0000-0003-4224-9245", "researcher": {"href": "https://publications.scilifelab.se/researcher/098ba38a51a64ba89362ed2a2e51455f.json"}}, {"family": "Davis", "given": "Lea K", "initials": "LK", "orcid": "0000-0001-5143-2282", "researcher": {"href": "https://publications.scilifelab.se/researcher/60132a034c8d412dbbb7fedbc9743d81.json"}}, {"family": "Stefansson", "given": "Hreinn", "initials": "H"}, {"family": "Stefansson", "given": "Kari", "initials": "K", "orcid": "0000-0003-1676-864X", "researcher": {"href": "https://publications.scilifelab.se/researcher/679465193fba4887a68e2aec34ccfd8e.json"}}, {"family": "Pedersen", "given": "Nancy L", "initials": "NL"}, {"family": "Ripke", "given": "Stephan", "initials": "S"}, {"family": "Andreassen", "given": "Ole A", "initials": "OA", "orcid": "0000-0002-4461-3568", "researcher": {"href": "https://publications.scilifelab.se/researcher/56f384e8e2fd4a7383c7b26e88a828b2.json"}}, {"family": "Posthuma", "given": "Danielle", "initials": "D", "orcid": "0000-0001-7582-2365", "researcher": {"href": "https://publications.scilifelab.se/researcher/406e98180d174e8ca087f50074c025c9.json"}}], "type": "journal article", "published": "2019-03-00", "journal": {"volume": "51", "issn": "1546-1718", "issue": "3", "pages": "404-413", "title": "Nat. Genet.", "issn-l": "1061-4036"}, "abstract": "Alzheimer's disease (AD) is highly heritable and recent studies have identified over 20 disease-associated genomic loci. Yet these only explain a small proportion of the genetic variance, indicating that undiscovered loci remain. Here, we performed a large genome-wide association study of clinically diagnosed AD and AD-by-proxy (71,880 cases, 383,378 controls). AD-by-proxy, based on parental diagnoses, showed strong genetic correlation with AD (rg = 0.81). Meta-analysis identified 29 risk loci, implicating 215 potential causative genes. Associated genes are strongly expressed in immune-related tissues and cell types (spleen, liver, and microglia). Gene-set analyses indicate biological mechanisms involved in lipid-related processes and degradation of amyloid precursor proteins. We show strong genetic correlations with multiple health-related outcomes, and Mendelian randomization results suggest a protective effect of cognitive ability on AD risk. These results are a step forward in identifying the genetic factors that contribute to AD risk and add novel insights into the neurobiology of AD.", "doi": "10.1038/s41588-018-0311-9", "pmid": "30617256", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (SNP&SEQ Technology Platform)": null}, "xrefs": [{"db": "mid", "key": "NIHMS1031924"}, {"db": "pmc", "key": "PMC6836675"}, {"db": "pii", "key": "10.1038/s41588-018-0311-9"}], "notes": [], "created": "2019-03-13T09:21:28.969Z", "modified": "2023-06-20T15:57:06.709Z"}]}