Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression.

Glanville, K.P.; Coleman, JRI; Hanscombe, K.B.; Euesden, J.; Choi, S.W.; Purves, K.L.; Breen, G.; Air, T.M.; Andlauer, TFM; Baune, B.T.; Binder, E.B.; Blackwood, DHR; Boomsma, D.I.; Buttenschøn, H.N.; Colodro-Conde, L.; Dannlowski, U.; Direk, N.; Dunn, E.C.; Forstner, A.J.; de Geus, EJC; Grabe, H.J.; Hamilton, S.P.; Jones, I.; Jones, L.A.; Knowles, J.A.; Kutalik, Z.; Levinson, D.F.; Lewis, G.; Lind, P.A.; Lucae, S.; Magnusson, P.K.; McGuffin, P.; McIntosh, A.M.; Milaneschi, Y.; Mors, O.; Mostafavi, S.; Müller-Myhsok, B.; Pedersen, N.L.; Penninx, BWJH; Potash, J.B.; Preisig, M.; Ripke, S.; Shi, J.; Shyn, S.I.; Smoller, J.W.; Streit, F.; Sullivan, P.F.; Tiemeier, H.; Uher, R.; Van der Auwera, S.; Weissman, M.M.; O'Reilly, P.F.; Lewis, C.M.

doi:10.1016/j.biopsych.2019.06.031

Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression.

Details

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Version: Final published version
License: CC BY 4.0

Serval ID

serval:BIB_1CD179C2A16D

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression.

Journal

Biological psychiatry

Author(s)

Glanville K.P., Coleman JRI, Hanscombe K.B., Euesden J., Choi S.W., Purves K.L., Breen G., Air T.M., Andlauer TFM, Baune B.T., Binder E.B., Blackwood DHR, Boomsma D.I., Buttenschøn H.N., Colodro-Conde L., Dannlowski U., Direk N., Dunn E.C., Forstner A.J., de Geus EJC, Grabe H.J., Hamilton S.P., Jones I., Jones L.A., Knowles J.A., Kutalik Z., Levinson D.F., Lewis G., Lind P.A., Lucae S., Magnusson P.K., McGuffin P., McIntosh A.M., Milaneschi Y., Mors O., Mostafavi S., Müller-Myhsok B., Pedersen N.L., Penninx BWJH, Potash J.B., Preisig M., Ripke S., Shi J., Shyn S.I., Smoller J.W., Streit F., Sullivan P.F., Tiemeier H., Uher R., Van der Auwera S., Weissman M.M., O'Reilly P.F., Lewis C.M.

Working group(s)

Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

Contributor(s)

Wray N.R., Ripke S., Mattheisen M., Trzaskowski M., Byrne E.M., Abdellaoui A., Adams M.J., Agerbo E., Air T.M., Andlauer TFM, Bacanu S.A., Bækvad-Hansen M., Beekman ATF, Bigdeli T.B., Binder E.B., Bryois J., Buttenschøn H.N., Bybjerg-Grauholm J., Cai N., Castelao E., Christensen J.H., Clarke T.K., Coleman JRI, Colodro-Conde L., Couvy-Duchesne B., Craddock N., Crawford G.E., Davies G., Deary I.J., Degenhardt F., Derks E.M., Direk N., Dolan C.V., Dunn E.C., Eley T.C., Escott-Price V., Hassan Kiadeh F.F., Finucane H.K., Foo J.C., Forstner A.J., Frank J., Gaspar H.A., Gill M., Goes F.S., Gordon S.D., Grove J., Hall L.S., Hansen C.S., Hansen T.F., Herms S., Hickie I.B., Hoffmann P., Homuth G., Horn C., Hottenga J.J., Hougaard D.M., Howard D.M., Ising M., Jansen R., Jones I., Jones L.A., Jorgenson E., Knowles J.A., Kohane I.S., Kraft J., Kretzschmar W.W., Kutalik Z., Li Y., Lind P.A., MacIntyre D.J., MacKinnon D.F., Maier R.M., Maier W., Marchini J., Mbarek H., McGrath P., McGuffin P., Medland S.E., Mehta D., Middeldorp C.M., Mihailov E., Milaneschi Y., Milani L., Mondimore F.M., Montgomery G.W., Mostafavi S., Mullins N., Nauck M., Ng B., Nivard M.G., Nyholt D.R., O'Reilly P.F., Oskarsson H., Owen M.J., Painter J.N., Pedersen C.B., Pedersen M.G., Peterson R.E., Pettersson E., Peyrot W.J., Pistis G., Posthuma D., Quiroz J.A., Qvist P., Rice J.P., Riley B.P., Rivera M., Mirza S.S., Schoevers R., Schulte E.C., Shen L., Shi J., Shyn S.I., Sigurdsson E., Sinnamon GCB, Smit J.H., Smith D.J., Stefansson H., Steinberg S., Streit F., Strohmaier J., Tansey K.E., Teismann H., Teumer A., Thompson W., Thomson P.A., Thorgeirsson T.E., Traylor M., Treutlein J., Trubetskoy V., Uitterlinden A.G., Umbricht D., Van der Auwera S., van Hemert A.M., Viktorin A., Visscher P.M., Wang Y., Webb B.T., Weinsheimer S.M., Wellmann J., Willemsen G., Witt S.H., Wu Y., Xi H.S., Yang J., Zhang F., Arolt V., Baune B.T., Berger K., Boomsma D.I., Cichon S., Dannlowski U., de Geus E., DePaulo J.R., Domenici E., Domschke K., Esko T., Grabe H.J., Hamilton S.P., Hayward C., Heath A.C., Kendler K.S., Kloiber S., Lewis G., Li Q.S., Lucae S., Madden P.A., Magnusson P.K., Martin N.G., McIntosh A.M., Metspalu A., Mors O., Mortensen P.B., Müller-Myhsok B., Nordentoft M., Nöthen M.M., O'Donovan M.C., Paciga S.A., Pedersen N.L., Penninx BWJH, Perlis R.H., Porteous D.J., Potash J.B., Preisig M., Rietschel M., Schaefer C., Schulze T.G., Smoller J.W., Stefansson K., Tiemeier H., Uher R., Völzke H., Weissman M.M., Werge T., Lewis C.M., Levinson D.F., Breen G., Børglum A.D., Sullivan P.F.

ISSN

1873-2402 (Electronic)

ISSN-L

0006-3223

Publication state

Published

Issued date

01/03/2020

Peer-reviewed

Oui

Volume

Number

Pages

419-430

Language

english

Notes

Publication types: Journal Article
Publication Status: ppublish

Abstract

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 <sup>-6</sup> ) and a candidate threshold (1.6 × 10 <sup>-4</sup> ).
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.

Keywords

Autoimmune disorder, Complement, Genetic association, Human leukocyte antigen, Major depressive disorder, Major histocompatibility complex

URN

urn:nbn:ch:serval-BIB_1CD179C2A16D2

OAI-PMH

oai:serval.unil.ch:BIB_1CD179C2A16D

DOI

10.1016/j.biopsych.2019.06.031

Pubmed

31570195

Web of science

000511835600008