Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression

Naomi R. Wray*, Stephan Ripke, Manuel Mattheisen, MacIej Trzaskowski, Enda M. Byrne, Abdel Abdellaoui, Mark J. Adams, Esben Agerbo, Tracy M. Air, Till M.F. Andlauer, Silviu Alin Bacanu, Marie Bækvad-Hansen, Aartjan F.T. Beekman, Tim B. Bigdeli, Elisabeth B. Binder, Douglas R.H. Blackwood, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, Na CaiEnrique Castelao, Jane Hvarregaard Christensen, Toni Kim Clarke, Jonathan I.R. Coleman, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E. Crawford, Cheynna A. Crowley, Hassan S. Dashti, Gail Davies, Ian J. Deary, Franziska Degenhardt, Eske M. Derks, Nese DIrek, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Nicholas Eriksson, Jouke Jan Hottenga, Rick Jansen, Hamdi Mbarek, Christel M. Middeldorp, Yuri Milaneschi, M. G. Nivard, Danielle Posthuma, Johannes H. Smit, G. Willemsen, Dorret I. Boomsma, Brenda W.J.H. Penninx

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

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Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.

Original languageEnglish
Pages (from-to)668-681
Number of pages14
JournalNature Genetics
Issue number5
Early online date26 Apr 2018
Publication statusPublished - May 2018


  • Journal Article

Cohort Studies

  • Netherlands Twin Register (NTR)


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