PT  - JOURNAL ARTICLE
AU  - David M. Howard
AU  - Mark J. Adams
AU  - Masoud Shirali
AU  - Toni-Kim Clarke
AU  - Riccardo E. Marioni
AU  - Gail Davies
AU  - Jonathan R. I. Coleman
AU  - Clara Alloza
AU  - Xueyi Shen
AU  - Miruna C. Barbu
AU  - Eleanor M. Wigmore
AU  - Jude Gibson
AU  - Saskia P. Hagenaars
AU  - Cathryn M. Lewis
AU  - Daniel J. Smith
AU  - Patrick F. Sullivan
AU  - Chris S. Haley
AU  - Gerome Breen
AU  - Ian J. Deary
AU  - Andrew M. McIntosh
TI  - Genome-wide association study of depression phenotypes in UK Biobank (n = 322,580) identifies the enrichment of variants in excitatory synaptic pathways
AID  - 10.1101/168732
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 168732
4099  - http://biorxiv.org/content/early/2017/08/01/168732.short
4100  - http://biorxiv.org/content/early/2017/08/01/168732.full
AB  - Depression is a polygenic trait that causes extensive periods of disability and increases the risk of suicide, a leading cause of death in young people. Previous genetic studies have identified a number of common risk variants which have increased in number in line with increasing sample sizes. We conducted a genome-wide association study (GWAS) in the largest single population-based cohort to date, UK Biobank. This allowed us to estimate the effects of ≈ 8 million genetic variants in 320,000 people for three depression phenotypes: broad depression, probable major depressive disorder (MDD), and International Classification of Diseases (ICD, version 9 or 10)-coded MDD. Each phenotype was found to be significantly genetically correlated with the results from a previous independent study of clinically defined MDD. We identified 14 independent loci that were significantly associated (P < 5 × 10−8) with broad depression, two independent variants for probable MDD, and one independent variant for ICD-coded MDD. Gene-based analysis of our GWAS results with MAGMA revealed 46 regions significantly associated (P < 2.77 × 10−6) with broad depression, two significant regions for probable MDD and one significant region for ICD-coded MDD. Gene region-based analysis of our GWAS results with MAGMA revealed 59 regions significantly associated (P < 6.02 × 10−6) with broad depression, of which 27 were also detected by gene-based analysis. Variants for broad depression were enriched in pathways for excitatory neurotransmission, mechanosensory behavior, postsynapse, neuron spine and dendrite. This study provides a number of novel genetic risk variants that can be leveraged to elucidate the mechanisms of MDD and low mood.