Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression.
Détails
Télécharger: 31570195_BIB_1CD179C2A16D.pdf (581.16 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_1CD179C2A16D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression.
Périodique
Biological psychiatry
Collaborateur⸱rice⸱s
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
Contributeur⸱rice⸱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
Statut éditorial
Publié
Date de publication
01/03/2020
Peer-reviewed
Oui
Volume
87
Numéro
5
Pages
419-430
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
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.
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.
Mots-clé
Autoimmune disorder, Complement, Genetic association, Human leukocyte antigen, Major depressive disorder, Major histocompatibility complex
Pubmed
Web of science
Open Access
Oui
Création de la notice
02/10/2019 15:45
Dernière modification de la notice
12/01/2022 7:08