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

• Authors: Naomi R Wray, University of Queensland; Stephan Ripke, Broad Institute; Manuel Mattheisen, Aarhus University; Maciej Trzaskowski, University of Queensland; Enda M Byrne, University of Queensland; Abdel Abdellaoui, Vrije Universiteit Amsterdam; Mark J Adams, University of Edinburgh; Esben Agerbo, Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH); Tracy M Air, University of Adelaide; Elisabeth Binder, Emory University
• Journal Title: Nature Genetics
• Volume: Volume 50, Number 5
• Publisher: Nature Research (part of Springer Nature) | 2018-05-01, Pages 668-+
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1038/s41588-018-0090-3
• Subjects: Psychology, Clinical
• Keywords: Science & Technology; Life Sciences & Biomedicine; Genetics & Heredity; LD SCORE REGRESSION; BODY-MASS INDEX; MENDELIAN RANDOMIZATION; EDUCATIONAL-ATTAINMENT; SYSTEMATIC ANALYSIS; MENTAL-DISORDERS; POLYGENIC RISK; EUROPE 2010; LOCI; METAANALYSIS

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 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.