Journal
NATURE GENETICS
Volume 50, Issue 5, Pages 668-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41588-018-0090-3
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Funding
- US National Institutes of Health [U01 MH109528, U01 MH109532]
- Lundbeck Foundation [R102-A9118, R155-2014-1724]
- Stanley Medical Research Institute
- European Research Council [294838]
- Novo Nordisk Foundation
- National Institute of Mental Health [R01 MH67257, R01 MH59588, R01 MH59571, R01 MH59565, R01 MH59587, R01 MH60870, R01 MH59566, R01 MH59586, R01 MH61675, R01 MH60879, R01 MH81800, U01 MH46276, U01 MH46289, U01 MH46318, U01 MH79469, U01 MH79470]
- NIH [P50 CA093459, P50 CA097007, R01 ES011740, R01 CA133996]
- MRC [MR/L023784/2, UKDRI-3003, G0200243, MR/N015746/1, MC_PC_U127561128, MC_UU_00007/10] Funding Source: UKRI
- Lundbeck Foundation [R248-2017-2003, R155-2014-1724] Funding Source: researchfish
- Medical Research Council [MR/L023784/2, MR/L010305/1, MC_qA137853, MC_PC_17228, MR/K026992/1, MC_UU_00007/10, MR/N015746/1, UKDRI-3003] Funding Source: researchfish
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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.
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