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dc.contributor.authorGill, Michaelen
dc.date.accessioned2020-03-07T14:44:23Z
dc.date.available2020-03-07T14:44:23Z
dc.date.issued2020en
dc.date.submitted2020en
dc.identifier.citationGlanville, Kylie P. ... [et al.]; Michael Gill, Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression, Biological Psychiatry, 87, March 1, 2020, 419 - 430en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/91728
dc.descriptionPUBLISHEDen
dc.description.abstractBACKGROUND: The prevalence of depression is higher in individuals with autoimmune diseases, but the mechanisms underlying the observed comorbidities are unknown. Shared genetic etiology is a plausible explanation for the overlap, and in this study we tested whether genetic variation in the major histocompatibility complex (MHC), which is associated with risk for autoimmune diseases, is also associated with risk for depression. METHODS: We fine-mapped the classical MHC (chr6: 29.6–33.1 Mb), imputing 216 human leukocyte antigen (HLA) alleles and 4 complement component 4 (C4) haplotypes in studies from the Psychiatric Genomics Consortium Major Depressive Disorder Working Group and the UK Biobank. The total sample size was 45,149 depression cases and 86,698 controls. We tested for association between depression status and imputed MHC variants, applying both a region-wide significance threshold (3.9 3 1026 ) and a candidate threshold (1.6 3 1024 ). RESULTS: No HLA alleles or C4 haplotypes were associated with depression at the region-wide threshold. HLAB*08:01 was associated with modest protection for depression at the candidate threshold for testing in HLA genes in the meta-analysis (odds ratio = 0.98, 95% confidence interval = 0.97–0.99). CONCLUSIONS: We found no evidence that an increased risk for depression was conferred by HLA alleles, which play a major role in the genetic susceptibility to autoimmune diseases, or C4 haplotypes, which are strongly associated with schizophrenia. These results suggest that any HLA or C4 variants associated with depression either are rare or have very modest effect sizes.en
dc.format.extent419en
dc.format.extent430en
dc.relation.ispartofseriesBiological Psychiatryen
dc.relation.ispartofseries87en
dc.relation.ispartofseriesMarch 1en
dc.rightsYen
dc.subjectAutoimmune disorderen
dc.subjectComplementen
dc.subjectGenetic associationen
dc.subjectHuman leukocyte antigenen
dc.subjectMajor depressive disorderen
dc.subjectMajor histocompatibility complexen
dc.titleClassical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depressionen
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/mgillen
dc.identifier.rssinternalid214726en
dc.identifier.doihttps://doi.org/10.1016/j.biopsych.2019.06.031en
dc.rights.ecaccessrightsopenAccess
dc.identifier.orcid_id0000-0003-0206-5337en


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