Genome-wide association study of depression phenotypes in UK Biobank identifies variants in excitatory synaptic pathways

David M. Howard*, Mark J. Adams, Masoud Shirali, Toni-Kim Clarke, Riccardo E. Marioni, Gail Davies, Jonathan R. I. Coleman, Clara Alloza, Xueyi Shen, Miruna C. Barbu, Eleanor M. Wigmore, Jude Gibson, 23andMe Research Team, Saskia P Hagenaars, Cathryn M. Lewis, Joey Ward, Daniel J Smith, Patrick F. Sullivan, Chris S. Haley, Gerome BreenIan J. Deary, Andrew M. McIntosh

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Depression is a polygenic trait that causes extensive periods of disability. Previous genetic studies have identified common risk variants which have progressively increased in number with increasing sample sizes of the respective studies. Here, we conduct a genome-wide association study in 322,580 UK Biobank participants for three depression-related phenotypes: broad depression, probable major depressive disorder (MDD), and International Classification of Diseases (ICD, version 9 or 10)-coded MDD. We identify 17 independent loci that are significantly associated (P < 5 × 10−8) across the three phenotypes. The direction of effect of these loci is consistently replicated in an independent sample, with 14 loci likely representing novel findings. Gene sets are enriched in excitatory neurotransmission, mechanosensory behaviour, post synapse, neuron spine and dendrite functions. Our findings suggest that broad depression is the most tractable UK Biobank phenotype for discovering genes and gene sets that further our understanding of the biological pathways underlying depression.
Original languageEnglish
Article number1470
Pages (from-to)1-10
Number of pages10
JournalNature Communications
Issue number1
Publication statusPublished - 16 Apr 2018

Keywords / Materials (for Non-textual outputs)

  • Biological Specimen Banks
  • Biomarkers/metabolism
  • Cohort Studies
  • Depression/genetics
  • Depressive Disorder, Major/genetics
  • Gene Expression Regulation
  • Genetic Loci
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • International Classification of Diseases
  • Linkage Disequilibrium
  • Mechanotransduction, Cellular/genetics
  • Nerve Tissue Proteins/genetics
  • Phenotype
  • Synapses/genetics
  • Synaptic Transmission/genetics
  • United Kingdom


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