| Title: | Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions |
| Journal: | Nature Neuroscience |
| Published: | 27 May 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34045744/ |
| DOI: | https://doi.org/10.1038/s41593-021-00860-2 |
| URL: | https://www.nature.com/articles/s41593-021-00860-2.pdf |
| Citations: | 254 (168 in last 2 years) as of 8 Aug 2024 |
Publication 4343
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Abstract
Major depressive disorder is the most common neuropsychiatric disorder, affecting 11% of veterans. Here we report results of a large meta-analysis of depression using data from the Million Veteran Program, 23andMe, UK Biobank and FinnGen, including individuals of European ancestry (n = 1,154,267; 340,591 cases) and African ancestry (n = 59,600; 25,843 cases). Transcriptome-wide association study analyses revealed significant associations with expression of NEGR1 in the hypothalamus and DRD2 in the nucleus accumbens, among others. We fine-mapped 178 genomic risk loci, and we identified likely pathogenicity in these variants and overlapping gene expression for 17 genes from our transcriptome-wide association study, including TRAF3. Finally, we were able to show substantial replications of our findings in a large independent cohort (n = 1,342,778) provided by 23andMe. This study sheds light on the genetic architecture of depression and provides new insight into the interrelatedness of complex psychiatric traits.</p>
18 Authors
- Daniel F. Levey
- Murray B. Stein
- Frank R. Wendt
- Gita A. Pathak
- Hang Zhou
- Mihaela Aslan
- Rachel Quaden
- Kelly M. Harrington
- Yaira Z. Nuñez
- Cassie Overstreet
- Krishnan Radhakrishnan
- Gerard Sanacora
- Andrew M. McIntosh
- Jingchunzi Shi
- Suyash S. Shringarpure
- John Concato
- Renato Polimanti
- Joel Gelernter
Enabling scientific discoveries that improve human health