TY - JOUR T1 - Genome-wide association study of depression phenotypes in UK Biobank (n = 322,580) identifies the enrichment of variants in excitatory synaptic pathways JF - bioRxiv DO - 10.1101/168732 SP - 168732 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 - 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 Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/07/26/168732.abstract N2 - 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 ≈ 20 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 12 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 52 regions significantly (P < 2.72 × 10−6) associated with broad depression, six regions in probable MDD and three regions in ICD-coded MDD. Gene region-based analysis of our GWAS results with MAGMA revealed 57 regions significantly (P < 6.01 × 10−6) associated with broad depression, of which 35 were also detected by gene-based analysis. Variants for broad depression were enriched in pathways for excitatory neurotransmission and neuron spines. This study provides a number of novel genetic risk variants that can be leveraged to elucidate the mechanisms of MDD and low mood. ER -