Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions.
David M Howard,
Mark J Adams,
Jonathan D. Hafferty,
Jonathan RI Coleman,
Saskia P Hagenaars,
Eleanor M. Wigmore,
Miruna C Barbu,
Eileen Y. Xu,
Heather C. Whalley,
Riccardo E Marioni,
David J Porteous,
Ian J Deary,
Bernhard T Baune,
David A. Hinds,
23andMe Research Team,
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium,
Enda M. Byrne,
Daniel J Smith,
Patrick F Sullivan,
Naomi R. Wray,
Cathryn M Lewis,
Posted 09 Oct 2018
bioRxiv DOI: 10.1101/433367 (published DOI: 10.1038/s41593-018-0326-7)
Posted 09 Oct 2018
Major depression is a debilitating psychiatric illness that is typically associated with low mood, anhedonia and a range of comorbidities. Depression has a heritable component that has remained difficult to elucidate with current sample sizes due to the polygenic nature of the disorder. To maximise sample size, we meta-analysed 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 gene-sets associated with depression, including both genes and gene-pathways associated with synaptic structure and neurotransmission. Further evidence of the importance of prefrontal brain regions in depression was provided by an enrichment analysis. 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 following multiple testing correction. Based on the putative genes associated with depression this work also highlights several potential drug repositioning opportunities. These findings advance our understanding of the complex genetic architecture of depression and provide several future avenues for understanding aetiology and developing new treatment approaches.
- Downloaded 4,520 times
- Download rankings, all-time:
- Site-wide: 2,280
- In genetics: 85
- Year to date:
- Site-wide: 36,480
- Since beginning of last month:
- Site-wide: 46,684
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!