RT Journal Article
SR Electronic
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
FD Cold Spring Harbor Laboratory
SP 168732
DO 10.1101/168732
A1 David M. Howard
A1 Mark J. Adams
A1 Masoud Shirali
A1 Toni-Kim Clarke
A1 Riccardo E. Marioni
A1 Gail Davies
A1 Jonathan R. I. Coleman
A1 Clara Alloza
A1 Xueyi Shen
A1 Miruna C. Barbu
A1 Eleanor M. Wigmore
A1 Jude Gibson
A1 Saskia P. Hagenaars
A1 Cathryn M. Lewis
A1 Daniel J. Smith
A1 Patrick F. Sullivan
A1 Chris S. Haley
A1 Gerome Breen
A1 Ian J. Deary
A1 Andrew M. McIntosh
YR 2017
UL http://biorxiv.org/content/early/2017/08/01/168732.abstract
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.