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
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