Journal
MOLECULAR PSYCHIATRY
Volume 20, Issue 6, Pages 735-743Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/mp.2015.50
Keywords
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Funding
- Australian Research Council [FT0991360, DE130100614]
- National Health and Medical Research Council [613608, 1011506, 1047956]
- National Institute of Mental Health (NIMH) [U01 MH085520]
- Netherlands Scientific Organization
- German Federal Ministry of Education and Research, within the context of the National Genome Research Network 2 (NGFN2)
- National Genome Research Network plus (NGFNplus)
- Integrated Genome Research Network (IG) MooDS [01GS08144, 01GS08147]
- European Union [LSHM-CT-2006-037761, PIAP-GA-2008-218251, HEALTH-F2-2009-223423]
- Medical Research Council (UK)
- Mental Health Research Network
- Innovative Medicines Initiative Joint Undertaking [115008]
- NIMH [MH061686, MH059542, MH075131, MH059552, MH059541, MH060912]
- Broad Institute Center for Genotyping and Analysis [U54 RR020278]
- GenRED
- NIMH
- National Alliance for Research on Schizophrenia and Depression
- Depression Genes and Networks ARRA grant [RC2MH089916]
- Harvard i2b2
- i2b2 Center
- NIH-funded National Center for Biomedical Computing based at Partners HealthCare System [U54LM008748]
- BMBF Program Molecular Diagnostics: Validation of Biomarkers for Diagnosis and Outcome in Major Depression [01ES0811]
- Bavarian Ministry of Commerce
- Federal Ministry of Education and Research (BMBF) [FKZ 01GS0481, 01GS08145]
- Netherlands Organization for Scientific Research (MagW/ZonMW) [904-61-090, 985-10-002, 904-61-193, 480-04- 004, 400-05-717, 912-100-20]
- Netherlands Organization for Scientific Research (Spinozapremie) [56-464-14192]
- Netherlands Organization for Scientific Research (Geestkracht program) [10-000-1002]
- Center for Medical Systems Biology (NWO Genomics), Biobanking and Biomolecular Resources Research Infrastructure, VU University's Institutes for Health and Care Research and Neuroscience Campus Amsterdam, NBIC/BioAssist/RK [2008.024]
- European Science Foundation [EU/QLRT-2001-01254]
- European Community's Seventh Framework Program
- ENGAGE [HEALTH-F4-2007-201413]
- European Science Council (ERC) [230374]
- Genetic Association Information Network (GAIN) of the Foundation for the US National Institutes of Health
- GAIN
- Swiss National Science Foundation [3200B0-105993, 3200B0-118'308, 33CSC0-122661]
- GlaxoSmithKline
- Australian National Health and Medical Research Council [613608, 241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496675, 496739, 552485, 552498, 613602, 613674, 619667]
- FP-5 GenomEUtwin Project [QLG2-CT-2002-01254]
- US National Institutes of Health [AA07535, AA10248, AA13320, AA13321, AA13326, AA14041, MH66206, DA12854, DA019951]
- Center for Inherited Disease Research (Baltimore, MD, USA)
- UK Medical Research Council and GlaxoSmithKline [G0701420]
- National Institute for Health Research (NIHR) Specialist Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and the Institute of Psychiatry, King's College London
- UK Medical Research Council [G0000647]
- European Commission [LSHB-CT-2003-503428]
- Federal Ministry of Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0403]
- Ministry of Cultural Affairs
- Social Ministry of the Federal State of Mecklenburg-West Pomerania
- Siemens Healthcare, Erlangen, Germany
- Federal State of Mecklenburg-West Pomerania
- German Research Foundation (DFG) [GR 1912/5-1]
- NIMH Grant [MH072802]
- National Institute of Mental Health [N01MH90003]
- Swedish Ministry for Higher Education
- Swedish Research Council [M-2005-1112]
- GenomEUtwin [EU/QLRT-2001-01254, QLG2-CT-2002-01254]
- Swedish Foundation for Strategic Research
- Wellcome Trust [076113, 085475]
- European Regional Development Fund [3.2.0304.11-0312]
- 'Center of Excellence in Genomics' (EXCEGEN)
- Estonian Government [IUT24-6, IUT20-60]
- CTG grant from Development Fund of the University of Tartu [SP1GVAR-ENG]
- National Health and Medical Research Early Career Fellowship Scheme
- [MH086026]
- [MH081802]
- [FT0991022]
- [03ZIK012]
- [U01 DK066134]
- [313010]
- MRC [G0701420] Funding Source: UKRI
- Swiss National Science Foundation (SNF) [33CSC0-122661] Funding Source: Swiss National Science Foundation (SNF)
- Chief Scientist Office [SCD/12] Funding Source: researchfish
- Lundbeck Foundation [R155-2014-1724] Funding Source: researchfish
- Medical Research Council [G0701420, 1201677] Funding Source: researchfish
- Australian Research Council [DE130100614] Funding Source: Australian Research Council
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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 similar to 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.
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