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

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The Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, 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 & 32 others Na Cai, Enrique 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, Thalia C. Eley, Héléna A. Gaspar, Thomas F. Hansen, Yun Li, Peter Mcguffin, Jonathan Mill, Niamh Mullins, Shaun M. Purcell, Brien P. Riley, Daniel J. Smith, Katherine E. Tansey, Matthew Traylor, Rudolf Uher, Cathryn M. Lewis, Gerome Breen, Paul F. O'Reilly

Original languageEnglish
Pages (from-to)668-681
JournalNature Genetics
Volume50
Issue number5
Early online date26 Apr 2018
DOIs
StatePublished - 1 May 2018

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Abstract

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 (GWA) meta-analysis based in 135,458 cases and 344,901 controls. We 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 relations 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 and define the basis of major depression and imply a continuous measure of risk underlies the clinical phenotype.

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