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

Peyrot WJ 1 , Lee SH 2 , Milaneschi Y 1 , Abdellaoui A 3 , Byrne EM 2 , Esko T 4 Show all authors , de Geus EJ 3 , Hemani G 5 , Hottenga JJ 3 , Kloiber S 6 , Levinson DF 7 , Lucae S 6 , Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium (Corporate Collaborator) , Martin NG 8 , Medland SE 8 , Metspalu A 4 , Milani L 4 , Noethen MM 9 , Potash JB 10 , Rietschel M 11 , Rietveld CA 12 , Ripke S 13 , Shi J 14 , Social Science Genetic Association Consortium Corporate Collaborator Willemsen G 3 , Zhu Z 2 , Boomsma DI 3 , Wray NR 2 , Penninx BW 1 , Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium Corporate Collaborator , Social Science Genetic Association Consortium Corporate Collaborator

Affiliations 

  • 1 Department of Psychiatry, VU University Medical Center and GGZ inGeest, Amsterdam, The Netherlands
  • 2 The University of Queensland, Queensland Brain Institute, Brisbane, Queensland, Australia
  • 3 Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands
  • 4 1] Estonian Genome Center, University of Tartu, Tartu, Estonia [2] Division of Endocrinology and Center of Basic and Translational Obesity Research, Children's Hospital Boston, Boston; Department of Genetics, Harvard Medical School, Boston; Broad Institute, Cambridge, MA, USA
  • 5 1] The University of Queensland, Queensland Brain Institute, Brisbane, Queensland, Australia [2] MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, School of Social and Community Medicine, Bristol, UK
  • 6 Max Planck Institute of Psychiatry, Munich, Germany
  • 7 Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA
  • 8 Genetic Epidemiology Unit, QIMR Berhgofer Institute of Medical Research, Brisbane, Queensland, Australia
  • 9 Institute of Human Genetics, University of Bonn, Bonn, Germany
  • 10 Department of Psychiatry, University of Iowa, Iowa City, IA, USA
  • 11 Department of Genetic Epidemiology in Psychiatry Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany
  • 12 1] Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, The Netherlands [2] Erasmus University Rotterdam Institute for Behavior and Biology, Erasmus University Rotterdam, Rotterdam, The Netherlands
  • 13 Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • 14 Biostatistics Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, MD, USA
Mol Psychiatry, 2015 Jun;20(6):735-43.
PMID: 25917368 DOI: 10.1038/mp.2015.50

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.

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