Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression
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Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression. / Glanville, Kylie P.; Coleman, Jonathan R.I.; Hanscombe, Ken B.; Euesden, Jack; Choi, Shing Wan; Purves, Kirstin L.; Breen, Gerome; Air, Tracy M.; Andlauer, Till F.M.; Baune, Bernhard T.; Binder, Elisabeth B.; Blackwood, Douglas H.R.; Boomsma, Dorret I.; Buttenschøn, Henriette N.; Colodro-Conde, Lucía; Dannlowski, Udo; Direk, Nese; Dunn, Erin C.; Forstner, Andreas J.; de Geus, Eco J.C.; Grabe, Hans J.; Hamilton, Steven P.; Jones, Ian; Jones, Lisa A.; Knowles, James A.; Kutalik, Zoltán; Levinson, Douglas F.; Lewis, Glyn; Lind, Penelope A.; Lucae, Susanne; Magnusson, Patrik K.; McGuffin, Peter; McIntosh, Andrew M.; Milaneschi, Yuri; Mors, Ole; Mostafavi, Sara; Müller-Myhsok, Bertram; Pedersen, Nancy L.; Penninx, Brenda W.J.H.; Potash, James B.; Preisig, Martin; Ripke, Stephan; Shi, Jianxin; Bækvad-Hansen, Marie; Hansen, Christine Søholm; Hansen, Thomas F.; Pedersen, Carsten Bøcker; Pedersen, Marianne Giørtz; Nordentoft, Merete; Werge, Thomas; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.
I: Biological Psychiatry, Bind 87, Nr. 5, 2020, s. 419-430.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression
AU - Glanville, Kylie P.
AU - Coleman, Jonathan R.I.
AU - Hanscombe, Ken B.
AU - Euesden, Jack
AU - Choi, Shing Wan
AU - Purves, Kirstin L.
AU - Breen, Gerome
AU - Air, Tracy M.
AU - Andlauer, Till F.M.
AU - Baune, Bernhard T.
AU - Binder, Elisabeth B.
AU - Blackwood, Douglas H.R.
AU - Boomsma, Dorret I.
AU - Buttenschøn, Henriette N.
AU - Colodro-Conde, Lucía
AU - Dannlowski, Udo
AU - Direk, Nese
AU - Dunn, Erin C.
AU - Forstner, Andreas J.
AU - de Geus, Eco J.C.
AU - Grabe, Hans J.
AU - Hamilton, Steven P.
AU - Jones, Ian
AU - Jones, Lisa A.
AU - Knowles, James A.
AU - Kutalik, Zoltán
AU - Levinson, Douglas F.
AU - Lewis, Glyn
AU - Lind, Penelope A.
AU - Lucae, Susanne
AU - Magnusson, Patrik K.
AU - McGuffin, Peter
AU - McIntosh, Andrew M.
AU - Milaneschi, Yuri
AU - Mors, Ole
AU - Mostafavi, Sara
AU - Müller-Myhsok, Bertram
AU - Pedersen, Nancy L.
AU - Penninx, Brenda W.J.H.
AU - Potash, James B.
AU - Preisig, Martin
AU - Ripke, Stephan
AU - Shi, Jianxin
AU - Bækvad-Hansen, Marie
AU - Hansen, Christine Søholm
AU - Hansen, Thomas F.
AU - Pedersen, Carsten Bøcker
AU - Pedersen, Marianne Giørtz
AU - Nordentoft, Merete
AU - Werge, Thomas
AU - Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
PY - 2020
Y1 - 2020
N2 - Background: 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 × 10−6) and a candidate threshold (1.6 × 10−4). Results: 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). 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.
AB - Background: 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 × 10−6) and a candidate threshold (1.6 × 10−4). Results: 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). 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.
KW - Autoimmune disorder
KW - Complement
KW - Genetic association
KW - Human leukocyte antigen
KW - Major depressive disorder
KW - Major histocompatibility complex
U2 - 10.1016/j.biopsych.2019.06.031
DO - 10.1016/j.biopsych.2019.06.031
M3 - Journal article
C2 - 31570195
AN - SCOPUS:85072749953
VL - 87
SP - 419
EP - 430
JO - Biological Psychiatry
JF - Biological Psychiatry
SN - 0006-3223
IS - 5
ER -
ID: 259048038