Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1038/s41593-018-0326-7

Type

Journal article

Journal

Nature neuroscience

Publication Date

03/2019

Volume

22

Pages

343 - 352

Addresses

Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK. D.Howard@ed.ac.uk.

Keywords

23andMe Research Team, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Prefrontal Cortex, Humans, Genetic Predisposition to Disease, Cohort Studies, Depression, Depressive Disorder, Major, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Female, Male, Genetic Variation, Genome-Wide Association Study