{"entity": "researcher", "timestamp": "2026-07-20T01:41:17.967Z", "family": "Ciuculete", "given": "Diana M", "initials": "DM", "orcid": "0000-0001-6377-0270", "affiliations": ["Department of Neuroscience, Functional Pharmacology, Uppsala University, BMC, Box 593, Husargatan 3, 753124, Uppsala, Sweden. diana-maria.ciuculete@neuro.uu.se."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/1facf036e83a4fd1934204cc1dc7ee4d.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/1facf036e83a4fd1934204cc1dc7ee4d"}}, "publications": [{"entity": "publication", "iuid": "125725b7b2fe4b5f8fc3e6674ca1d421", "links": {"self": {"href": "https://publications.scilifelab.se/publication/125725b7b2fe4b5f8fc3e6674ca1d421.json"}, "display": {"href": "https://publications.scilifelab.se/publication/125725b7b2fe4b5f8fc3e6674ca1d421"}}, "title": "Challenges in Analyzing Functional Epigenetic Data in Perspective of Adolescent Psychiatric Health.", "authors": [{"family": "Manu", "given": "Diana M", "initials": "DM", "orcid": "0000-0001-6377-0270", "researcher": {"href": "https://publications.scilifelab.se/researcher/1facf036e83a4fd1934204cc1dc7ee4d.json"}}, {"family": "Mwinyi", "given": "Jessica", "initials": "J"}, {"family": "Schi\u00f6th", "given": "Helgi B", "initials": "HB"}], "type": "journal article", "published": "2022-05-23", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "volume": "23", "issue": "10", "issn-l": null}, "abstract": "The formative period of adolescence plays a crucial role in the development of skills and abilities for adulthood. Adolescents who are affected by mental health conditions are at risk of suicide and social and academic impairments. Gene-environment complementary contributions to the molecular mechanisms involved in psychiatric disorders have emphasized the need to analyze epigenetic marks such as DNA methylation (DNAm) and non-coding RNAs. However, the large and diverse bioinformatic and statistical methods, referring to the confounders of the statistical models, application of multiple-testing adjustment methods, questions regarding the correlation of DNAm across tissues, and sex-dependent differences in results, have raised challenges regarding the interpretation of the results. Based on the example of generalized anxiety disorder (GAD) and depressive disorder (MDD), we shed light on the current knowledge and usage of methodological tools in analyzing epigenetics. Statistical robustness is an essential prerequisite for a better understanding and interpretation of epigenetic modifications and helps to find novel targets for personalized therapeutics in psychiatric diseases.", "doi": "10.3390/ijms23105856", "pmid": "35628666", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "NGI SNP genotyping": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pii", "key": "ijms23105856"}], "notes": [], "created": "2022-06-14T13:16:29.585Z", "modified": "2022-06-14T13:16:29.624Z"}, {"entity": "publication", "iuid": "a1d31987288449ba8a738404fa44921b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a1d31987288449ba8a738404fa44921b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a1d31987288449ba8a738404fa44921b"}}, "title": "meQTL and ncRNA functional analyses of 102 GWAS-SNPs associated with depression implicate HACE1 and SHANK2 genes.", "authors": [{"family": "Ciuculete", "given": "Diana M", "initials": "DM", "orcid": "0000-0001-6377-0270", "researcher": {"href": "https://publications.scilifelab.se/researcher/1facf036e83a4fd1934204cc1dc7ee4d.json"}}, {"family": "Voisin", "given": "Sarah", "initials": "S"}, {"family": "Kular", "given": "Lara", "initials": "L"}, {"family": "Jonsson", "given": "J\u00f6rgen", "initials": "J"}, {"family": "Rask-Andersen", "given": "Mathias", "initials": "M"}, {"family": "Mwinyi", "given": "Jessica", "initials": "J"}, {"family": "Schi\u00f6th", "given": "Helgi B", "initials": "HB"}], "type": "journal article", "published": "2020-07-02", "journal": {"title": "Clin Epigenetics", "issn": "1868-7083", "volume": "12", "issue": "1", "pages": "99", "issn-l": "1868-7075"}, "abstract": "Little is known about how genetics and epigenetics interplay in depression. Evidence suggests that genetic variants may change vulnerability to depression by modulating DNA methylation (DNAm) and non-coding RNA (ncRNA) levels. Therefore, the aim of the study was to investigate the effect of the genetic variation, previously identified in the largest genome-wide association study for depression, on proximal DNAm and ncRNA levels.\n\nWe performed DNAm quantitative trait locus (meQTL) analysis in two independent cohorts (total n = 435 healthy individuals), testing associations between 102 single-nucleotide polymorphisms (SNPs) and DNAm levels in whole blood. We identified and replicated 64 SNP-CpG pairs (padj. < 0.05) with meQTL effect. Lower DNAm at cg02098413 located in the HACE1 promoter conferred by the risk allele (C allele) at rs1933802 was associated with higher risk for depression (praw = 0.014, DNAm = 2.3%). In 1202 CD14+ cells sorted from blood, DNAm at cg02088412 positively correlated with HACE1 mRNA expression. Investigation in postmortem brain tissue of adults diagnosed with major depressive disorder (MDD) indicated 1% higher DNAm at cg02098413 in neurons and lower HACE1 mRNA expression in CA1 hippocampus of MDD patients compared with healthy controls (p = 0.008 and 0.012, respectively). Expression QTL analysis in blood of 74 adolescent revealed that hsa-miR-3664-5p was associated with rs7117514 (SHANK2) (padj. = 0.015, mRNA difference = 5.2%). Gene ontology analysis of the miRNA target genes highlighted implication in neuronal processes.\n\nCollectively, our findings from a multi-tissue (blood and brain) and multi-layered (genetic, epigenetic, transcriptomic) approach suggest that genetic factors may influence depression by modulating DNAm and miRNA levels. Alterations at HACE1 and SHANK2 loci imply potential mechanisms, such as oxidative stress in the brain, underlying depression. Our results deepened the knowledge of molecular mechanisms in depression and suggest new epigenetic targets that should be further evaluated.", "doi": "10.1186/s13148-020-00884-8", "pmid": "32616021", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s13148-020-00884-8"}, {"db": "pmc", "key": "PMC7333393"}], "notes": [], "created": "2020-08-04T14:50:04.126Z", "modified": "2024-01-16T13:48:42.216Z"}, {"entity": "publication", "iuid": "ad8084cfea9d4cbfb73fec4819833186", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ad8084cfea9d4cbfb73fec4819833186.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ad8084cfea9d4cbfb73fec4819833186"}}, "title": "Longitudinal DNA methylation changes at MET may alter HGF/c-MET signalling in adolescents at risk for depression.", "authors": [{"family": "Ciuculete", "given": "Diana M", "initials": "DM", "orcid": "0000-0001-6377-0270", "researcher": {"href": "https://publications.scilifelab.se/researcher/1facf036e83a4fd1934204cc1dc7ee4d.json"}}, {"family": "Voisin", "given": "Sarah", "initials": "S", "orcid": "0000-0002-4074-7083", "researcher": {"href": "https://publications.scilifelab.se/researcher/3c6eab1a09084c1499c442d89bd2ff83.json"}}, {"family": "Kular", "given": "Lara", "initials": "L"}, {"family": "Welihinda", "given": "Nipuni", "initials": "N"}, {"family": "Jonsson", "given": "J\u00f6rgen", "initials": "J"}, {"family": "Jagodic", "given": "Maja", "initials": "M"}, {"family": "Mwinyi", "given": "Jessica", "initials": "J"}, {"family": "Schi\u00f6th", "given": "Helgi B", "initials": "HB"}], "type": "journal article", "published": "2019-12-19", "journal": {"volume": "15", "issn": "1559-2308", "issue": "6-7", "pages": "646-663", "title": "Epigenetics", "issn-l": "1559-2294"}, "abstract": "Unrecognized depression during adolescence can result in adult suicidal behaviour. The aim of this study was to identify, replicate and characterize DNA methylation (DNAm) shifts in depression aetiology, using a longitudinal, multi-tissue (blood and brain) and multi-layered (genetics, epigenetics, transcriptomics) approach. We measured genome-wide blood DNAm data at baseline and one-year follow-up, and imputed genetic variants, in 59 healthy adolescents comprising the discovery cohort. Depression and suicidal symptoms were determined using the Development and Well-Being Assessment (DAWBA) depression band, Montgomery-\u00c5sberg Depression Rating Scale-Self (MADRS-S) and SUicide Assessment Scale (SUAS). DNAm levels at follow-up were regressed against depression scores, adjusting for sex, age and the DNAm residuals at baseline. Higher methylation levels of 5% and 13% at cg24627299 within the MET gene were associated with higher depression scores (praw<1e-4) and susceptibility for suicidal symptoms (padj.<0.005). The nearby rs39748 was discovered to be a methylation and expression quantitative trait locus in blood cells. mRNA levels of hepatocyte growth factor (HGF) expression, known to strongly interact with MET, were inversely associated with methylation levels at cg24627299, in an independent cohort of 1180 CD14+ samples. In an open-access dataset of brain tissue, lower methylation at cg24627299 was found in 45 adults diagnosed with major depressive disorder compared with matched controls (padj.<0.05). Furthermore, lower MET expression was identified in the hippocampus of depressed individuals compared with controls in a fourth, independent cohort. Our findings reveal methylation changes at MET in the pathology of depression, possibly involved in downregulation of HGF/c-MET signalling the hippocampal region.", "doi": "10.1080/15592294.2019.1700628", "pmid": "31852353", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7574381"}], "notes": [], "created": "2020-01-07T14:39:03.531Z", "modified": "2024-01-16T13:48:43.281Z"}]}