The association between lower educational attainment and depression owing to shared genetic effects? Results in ~25,000 subjects.

TitleThe association between lower educational attainment and depression owing to shared genetic effects? Results in ~25,000 subjects.
Publication TypeJournal Article
Year of Publication2015
AuthorsPeyrot, WJ, Lee, SH, Milaneschi, Y, Abdellaoui, A, Byrne, EM, Esko, T, de Geus, EJC, Hemani, G, Hottenga, J-J, Kloiber, S, Levinson, DF, Lucae, S, Martin, NG, Medland, SE, Metspalu, A, Milani, L, Noethen, MM, Potash, JB, Rietschel, M, Rietveld, CA, Ripke, S, Shi, J, Willemsen, G, Zhu, Z, Boomsma, DI, Wray, NR, Penninx, BW
Corporate AuthorsMajor Depressive Disorder Working Group of the Psychiatric GWAS Consortium (Corporate Collaborator), Social Science Genetic Association Consortium Corporate Collaborator, Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium (Corporate Collaborator), Social Science Genetic Association Consortium Corporate Collaborator
JournalMolecular Psychiatry
Volume20
Issue6
Pagination735-43
Date Published2015 Jun
ISSN Number1476-5578
KeywordsDepressive symptoms, Education, Genetics, Mental Illness, Older Adults
Abstract

An association between lower educational attainment (EA) and an increased risk for depression has been confirmed in various western countries. This study examines whether pleiotropic genetic effects contribute to this association. Therefore, data were analyzed from a total of 9662 major depressive disorder (MDD) cases and 14,949 controls (with no lifetime MDD diagnosis) from the Psychiatric Genomics Consortium with additional Dutch and Estonian data. The association of EA and MDD was assessed with logistic regression in 15,138 individuals indicating a significantly negative association in our sample with an odds ratio for MDD 0.78 (0.75-0.82) per standard deviation increase in EA. With data of 884,105 autosomal common single-nucleotide polymorphisms (SNPs), three methods were applied to test for pleiotropy between MDD and EA: (i) genetic profile risk scores (GPRS) derived from training data for EA (independent meta-analysis on ~120,000 subjects) and MDD (using a 10-fold leave-one-out procedure in the current sample), (ii) bivariate genomic-relationship-matrix restricted maximum likelihood (GREML) and (iii) SNP effect concordance analysis (SECA). With these methods, we found (i) that the EA-GPRS did not predict MDD status, and MDD-GPRS did not predict EA, (ii) a weak negative genetic correlation with bivariate GREML analyses, but this correlation was not consistently significant, (iii) no evidence for concordance of MDD and EA SNP effects with SECA analysis. To conclude, our study confirms an association of lower EA and MDD risk, but this association was not because of measurable pleiotropic genetic effects, which suggests that environmental factors could be involved, for example, socioeconomic status.

DOI10.1038/mp.2015.50
Alternate JournalMol. Psychiatry
Citation Key8619
PubMed ID25917368
PubMed Central IDPMC4610719
Grant List076113 / / Wellcome Trust / United Kingdom
085475 / / Wellcome Trust / United Kingdom
104036 / / Wellcome Trust / United Kingdom
AA07535 / AA / NIAAA NIH HHS / United States
AA10248 / AA / NIAAA NIH HHS / United States
AA13320 / AA / NIAAA NIH HHS / United States
AA13321 / AA / NIAAA NIH HHS / United States
AA13326 / AA / NIAAA NIH HHS / United States
AA14041 / AA / NIAAA NIH HHS / United States
DA019951 / DA / NIDA NIH HHS / United States
DA12854 / DA / NIDA NIH HHS / United States
G0000647 / / Medical Research Council / United Kingdom
G0701420 / / Medical Research Council / United Kingdom
K08 DA019951 / DA / NIDA NIH HHS / United States
MH059541 / MH / NIMH NIH HHS / United States
MH059542 / MH / NIMH NIH HHS / United States
MH059552 / MH / NIMH NIH HHS / United States
MH060912 / MH / NIMH NIH HHS / United States
MH061686 / MH / NIMH NIH HHS / United States
MH072802 / MH / NIMH NIH HHS / United States
MH075131 / MH / NIMH NIH HHS / United States
MH081802 / MH / NIMH NIH HHS / United States
MH66206 / MH / NIMH NIH HHS / United States
N01 MH090003 / MH / NIMH NIH HHS / United States
N01MH90003 / MH / NIMH NIH HHS / United States
R01 AA007535 / AA / NIAAA NIH HHS / United States
R01 AA010249 / AA / NIAAA NIH HHS / United States
R01 AA013320 / AA / NIAAA NIH HHS / United States
R01 AA013321 / AA / NIAAA NIH HHS / United States
R01 AA013326 / AA / NIAAA NIH HHS / United States
R01 AA014041 / AA / NIAAA NIH HHS / United States
R01 AG017917 / AG / NIA NIH HHS / United States
R01 DA012854 / DA / NIDA NIH HHS / United States
R01 MH059542 / MH / NIMH NIH HHS / United States
R01 MH061686 / MH / NIMH NIH HHS / United States
R01 MH066206 / MH / NIMH NIH HHS / United States
R01 MH072802 / MH / NIMH NIH HHS / United States
R01 MH075131 / MH / NIMH NIH HHS / United States
R01 MH081802 / MH / NIMH NIH HHS / United States
R01 MH086026 / MH / NIMH NIH HHS / United States
R25 MH060482 / MH / NIMH NIH HHS / United States
R37 DA005147 / DA / NIDA NIH HHS / United States
RC2 MH089916 / MH / NIMH NIH HHS / United States
RC2MH089916 / MH / NIMH NIH HHS / United States
U01 DK066134 / DK / NIDDK NIH HHS / United States
U01 DK066134 / DK / NIDDK NIH HHS / United States
U01 MH085520 / MH / NIMH NIH HHS / United States
U01 MH085520 / MH / NIMH NIH HHS / United States
U54 LM008748 / LM / NLM NIH HHS / United States
U54 RR020278 / RR / NCRR NIH HHS / United States
U54 RR020278 / RR / NCRR NIH HHS / United States
U54LM008748 / LM / NLM NIH HHS / United States