TY - JOUR
T1 - Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions
AU - 23andMe Research Team
AU - the Million Veteran Program
AU - Levey, Daniel F.
AU - Stein, Murray B.
AU - Wendt, Frank R.
AU - Pathak, Gita A.
AU - Zhou, Hang
AU - Aslan, Mihaela
AU - Quaden, Rachel
AU - Harrington, Kelly M.
AU - Nuñez, Yaira Z.
AU - Overstreet, Cassie
AU - Radhakrishnan, Krishnan
AU - Sanacora, Gerard
AU - McIntosh, Andrew M.
AU - Shi, Jingchunzi
AU - Shringarpure, Suyash S.
AU - Concato, John
AU - Polimanti, Renato
AU - Gelernter, Joel
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2021/7
Y1 - 2021/7
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85107153807
U2 - 10.1038/s41593-021-00860-2
DO - 10.1038/s41593-021-00860-2
M3 - Article
C2 - 34045744
AN - SCOPUS:85107153807
SN - 1097-6256
VL - 24
SP - 954
EP - 963
JO - Nature Neuroscience
JF - Nature Neuroscience
IS - 7
ER -