Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions.
Nat Neurosci
; 24(7): 954-963, 2021 07.
Article
em En
| MEDLINE
| ID: mdl-34045744
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Predisposição Genética para Doença
/
Transtorno Depressivo Maior
Tipo de estudo:
Prognostic_studies
/
Systematic_reviews
Limite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Nat Neurosci
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos