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

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  • 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 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
  • Conor V Dolan
  • Erin C Dunn
  • Thalia C Eley
  • Nicholas Eriksson
  • Valentina Escott-Price
  • Farnush Hassan Farhadi Kiadeh
  • Hilary K Finucane
  • Andreas J Forstner
  • Josef Frank
  • Thomas F Hansen
  • Jesper Krogh
  • Wesley Thompson
  • Shantel Marie Weinsheimer
  • Merete Nordentoft
  • Thomas Werge
  • eQTLGen
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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
JournalNature Genetics
Volume50
Issue number5
Pages (from-to)668-681
Number of pages14
ISSN1061-4036
DOIs
Publication statusPublished - May 2018

ID: 55040817