RT Journal Article
T1 Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression.
A1 Glanville, Kylie P
A1 Coleman, Jonathan R I
A1 Hanscombe, Ken B
A1 Euesden, Jack
A1 Choi, Shing Wan
A1 Purves, Kirstin L
A1 Breen, Gerome
A1 Air, Tracy M
A1 Andlauer, Till F M
A1 Baune, Bernhard T
A1 Binder, Elisabeth B
A1 Blackwood, Douglas H R
A1 Boomsma, Dorret I
A1 Buttenschøn, Henriette N
A1 Colodro-Conde, Lucía
A1 Dannlowski, Udo
A1 Direk, Nese
A1 Dunn, Erin C
A1 Forstner, Andreas J
A1 de Geus, Eco J C
A1 Grabe, Hans J
A1 Hamilton, Steven P
A1 Jones, Ian
A1 Jones, Lisa A
A1 Knowles, James A
A1 Kutalik, Zoltán
A1 Levinson, Douglas F
A1 Lewis, Glyn
A1 Lind, Penelope A
A1 Lucae, Susanne
A1 Magnusson, Patrik K
A1 McGuffin, Peter
A1 McIntosh, Andrew M
A1 Milaneschi, Yuri
A1 Mors, Ole
A1 Mostafavi, Sara
A1 Müller-Myhsok, Bertram
A1 Pedersen, Nancy L
A1 Penninx, Brenda W J H
A1 Potash, James B
A1 Preisig, Martin
A1 Ripke, Stephan
A1 Shi, Jianxin
A1 Shyn, Stanley I
A1 Smoller, Jordan W
A1 Streit, Fabian
A1 Sullivan, Patrick F
A1 Tiemeier, Henning
A1 Uher, Rudolf
A1 Van der Auwera, Sandra
A1 Weissman, Myrna M
A1 Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, 
A1 O'Reilly, Paul F
A1 Lewis, Cathryn M
K1 Autoimmune disorder
K1 Complement
K1 Genetic association
K1 Human leukocyte antigen
K1 Major depressive disorder
K1 Major histocompatibility complex
AB 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. 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 × 10-6) and a candidate threshold (1.6 × 10-4). No HLA alleles or C4 haplotypes were associated with depression at the region-wide threshold. HLA-B*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). 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.
YR 2019
FD 2019-08-05
LK https://hdl.handle.net/10668/27676
UL https://hdl.handle.net/10668/27676
LA en
DS RISalud
RD Apr 17, 2025