RT Journal Article
SR Electronic
T1 Genetic variation in the Major Histocompatibility Complex and association with depression
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 469023
DO 10.1101/469023
A1 Kylie P Glanville
A1 Jonathan R I Coleman
A1 Ken B Hanscombe
A1 Jack Euesden
A1 Shing Wan Choi
A1 Kirstin L Purves
A1 Gerome Breen
A1 Tracy M Air
A1 Till F M Andlauer
A1 Bernhard T Baune
A1 Elisabeth B Binder
A1 Douglas H R Blackwood
A1 Dorret I Boomsma
A1 Henriette N Buttenschøn
A1 Lucía Colodro-Conde
A1 Udo Dannlowski
A1 Nese Direk
A1 Erin C Dunn
A1 Andreas J Forstner
A1 Eco JC de Geus
A1 Hans J Grabe
A1 Steven P Hamilton
A1 Ian Jones
A1 Lisa A Jones
A1 James A Knowles
A1 Zoltán Kutalik
A1 Douglas F Levinson
A1 Glyn Lewis
A1 Penelope A Lind
A1 Susanne Lucae
A1 Patrik K Magnusson
A1 Peter McGuffin
A1 Andrew M McIntosh
A1 Yuri Milaneschi
A1 Ole Mors
A1 Sara Mostafavi
A1 Bertram Müller-Myhsok
A1 Nancy L Pedersen
A1 Brenda WJH Penninx
A1 James B Potash
A1 Martin Preisig
A1 Stephan Ripke
A1 Jianxin Shi
A1 Stanley I Shyn
A1 Jordan W Smoller
A1 Fabian Streit
A1 Patrick F Sullivan
A1 Henning Tiemeier
A1 Rudolf Uher
A1 Sandra Van der Auwera
A1 Myrna M Weissman
A1 Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
A1 Paul F O’Reilly
A1 Cathryn M Lewis
YR 2018
UL http://biorxiv.org/content/early/2018/11/19/469023.abstract
AB Background The prevalence of depression is higher in individuals suffering from autoimmune diseases, but the mechanisms underlying the observed comorbidities are unknown. Epidemiological findings point to a bi-directional relationship - that depression increases the risk of developing an autoimmune disease, and vice-versa. Shared genetic etiology is a plausible explanation for the overlap between depression and autoimmune diseases. 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.Method We fine-mapped the classical MHC (chr6: 29.6-33.1 Mb), imputing 216 Human Leukocyte Antigen (HLA) alleles and four Complement Component 4 (C4) haplotypes in studies from the Psychiatric Genomics Consortium (PGC) Major Depressive Disorder (MDD) working group and the UK Biobank (UKB). In the 26 PGC-MDD studies, cases met a lifetime diagnosis of MDD, determined by a structured diagnostic interview. In the UKB, cases and controls were identified from an online mental health questionnaire. The total sample size was 45,149 depression cases and 86,698 controls. We tested for association between depression status and imputed MHC variants in each study and performed an inverse-variance weighted meta-analysis across the PGC-MDD and UKB samples, applying both a conservative region-wide significance threshold (3.9-e6) and a candidate threshold (1.6e-4).Results No HLA alleles or C4 haplotypes were associated with depression at the conservative threshold in the PGC, UKB or meta-analysis. HLA-B*08:01 was associated with modest protection for depression at the candidate threshold in the meta-analysis. Under the conservative threshold, 70 SNPs were detected in the UKB and 143 SNPs were detected in the meta-analysis, mirroring previous findings from highly powered GWAS of depression.Discussion We found no evidence that HLA alleles, which play a major role in the genetic susceptibility to autoimmune diseases, or C4 haplotypes, which are strongly associated with schizophrenia, confer risk for depression. These results indicate that autoimmune diseases and depression do not share common risk loci of moderate or large effect in the MHC.