Trans-ancestry genome-wide study of depression identifies 697 associations implicating cell types and pharmacotherapies

In a genome-wide association study (GWAS) meta-analysis of 688,808 individuals with major depression (MD) and 4,364,225 controls from 29 countries across diverse and admixed ancestries, we identify 697 associations at 635 loci, 293 of which are novel. Using fine-mapping and functional tools, we find 308 high-confidence gene associations and enrichment of postsynaptic density and receptor clustering. A neural cell-type enrichment analysis utilizing single-cell data implicates excitatory, inhibitory, and medium spiny neurons and the involvement of amygdala neurons in both mouse and human single-cell analyses. The associations are enriched for antidepressant targets and provide potential repurposing…

• FF
  Foundation for the National Institutes of Health
• OO
  Office of Research and Development
• NU
  Northwestern University
• SM
  Stanley Medical Research Institute
• WT
  Wellcome Trust
• NI
  National Institute for Health and Care Research
• DO
  Department of Health and Social Care
• KC
  King's College London
• EC
  European Commission

  Awards: 948561, 847776
• L
  Lundbeckfonden

  Awards: R155-2014-1724, R102-A9118
• NN
  Novo Nordisk
• NN
  Novo Nordisk Fonden
• HL
  H. Lundbeck A/S
• NI
  National Institutes of Health

  Awards: ES011740, CA093459
• RR
  Rehabilitation Research and Development Service
• H2
  Horizon 2020 Framework Programme
• NB
  NIHR BioResource
• NM
  NIHR Maudsley Biomedical Research Centre
• MR
  Medical Research Council

  Awards: MC_PC_14135, MC_UU_00017/1, MR/R023484/1, MR/Y011112/1, MR/L010305/1, MR/P00167X/1, MR/R004609/1
• EA
  Engineering and Physical Sciences Research Council

  Awards: EP/R00661X/1, EP/S019367/1, EP/X527257/1
• NG
  NODAI Genome Research Center, Tokyo University of Agriculture
• NI
  National Institute of Neurological Disorders and Stroke