| Literature DB >> 30718901 |
David M Howard1, Mark J Adams2, Toni-Kim Clarke2, Jonathan D Hafferty2, Jude Gibson2, Masoud Shirali2, Jonathan R I Coleman3,4, Saskia P Hagenaars3,4, Joey Ward5, Eleanor M Wigmore2, Clara Alloza2, Xueyi Shen2, Miruna C Barbu2, Eileen Y Xu2, Heather C Whalley2, Riccardo E Marioni6,7, David J Porteous6,7, Gail Davies6,8, Ian J Deary6,8, Gibran Hemani9, Klaus Berger10, Henning Teismann10, Rajesh Rawal10, Volker Arolt11, Bernhard T Baune12, Udo Dannlowski11, Katharina Domschke13, Chao Tian14, David A Hinds14, Maciej Trzaskowski15, Enda M Byrne15, Stephan Ripke16,17,18, Daniel J Smith5, Patrick F Sullivan19,20,21, Naomi R Wray15, Gerome Breen3,4, Cathryn M Lewis3,4, Andrew M McIntosh2,8.
Abstract
Major depression is a debilitating psychiatric illness that is typically associated with low mood and anhedonia. Depression has a heritable component that has remained difficult to elucidate with current sample sizes due to the polygenic nature of the disorder. To maximize sample size, we meta-analyzed data on 807,553 individuals (246,363 cases and 561,190 controls) from the three largest genome-wide association studies of depression. We identified 102 independent variants, 269 genes, and 15 genesets associated with depression, including both genes and gene pathways associated with synaptic structure and neurotransmission. An enrichment analysis provided further evidence of the importance of prefrontal brain regions. In an independent replication sample of 1,306,354 individuals (414,055 cases and 892,299 controls), 87 of the 102 associated variants were significant after multiple testing correction. These findings advance our understanding of the complex genetic architecture of depression and provide several future avenues for understanding etiology and developing new treatment approaches.Entities:
Mesh：
Year: 2019 PMID： 30718901 PMCID： PMC6522363 DOI： 10.1038/s41593-018-0326-7
Source DB: PubMed Journal: Nat Neurosci ISSN： 1097-6256 Impact factor: 28.771