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

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  • Jonathan R. I. Coleman
  • Clara Alloza
  • Miruna Barbu
  • Eleanor Wigmore
  • Jude Gibson
  • Saskia P Hagenaars
  • Cathryn M. Lewis
  • Joey Ward
  • Daniel J Smith
  • Patrick F. Sullivan
  • Gerome Breen

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https://www.nature.com/articles/s41467-018-03819-3
Original languageEnglish
Article number1470
Pages (from-to)1-10
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 16 Apr 2018

Abstract

Depression is a polygenic trait that causes extensive periods of disability. Previous genetic studies have identified a number of common risk variants which have progressively increased in number in line with increasing sample sizes of the respective studies. Here, We conducted a genome-wide association study in approximately 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 identifyied 17 independent loci that are significantly associated (P < 5 × 10-8) across the three phenotypes. The direction of effect of these loci consistently replicated in an independent sample , with 14 loci likely to representing novel findings. Gene sets are enriched in excitatory neurotransmission, mechanosensory behavior, postsynapse, neuron spine, and dendrite gene-sets functions were also identified. 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.

    Research areas

  • 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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