Genome-wide meta-analysis, functional genomics and integrative analyses implicate new risk genes and therapeutic targets for anxiety disorders.
Journal
Nature human behaviour
ISSN: 2397-3374
Titre abrégé: Nat Hum Behav
Pays: England
ID NLM: 101697750
Informations de publication
Date de publication:
09 Nov 2023
09 Nov 2023
Historique:
received:
19
02
2023
accepted:
04
10
2023
medline:
10
11
2023
pubmed:
10
11
2023
entrez:
9
11
2023
Statut:
aheadofprint
Résumé
Anxiety disorders are the most prevalent mental disorders. However, the genetic etiology of anxiety disorders remains largely unknown. Here we conducted a genome-wide meta-analysis on anxiety disorders by including 74,973 (28,392 proxy) cases and 400,243 (146,771 proxy) controls. We identified 14 risk loci, including 10 new associations near CNTNAP5, MAP2, RAB9BP1, BTN1A1, PRR16, PCLO, PTPRD, FARP1, CDH2 and RAB27B. Functional genomics and fine-mapping pinpointed the potential causal variants, and expression quantitative trait loci analysis revealed the potential target genes regulated by the risk variants. Integrative analyses, including transcriptome-wide association study, proteome-wide association study and colocalization analyses, prioritized potential causal genes (including CTNND1 and RAB27B). Evidence from multiple analyses revealed possibly causal genes, including RAB27B, BTN3A2, PCLO and CTNND1. Finally, we showed that Ctnnd1 knockdown affected dendritic spine density and resulted in anxiety-like behaviours in mice, revealing the potential role of CTNND1 in anxiety disorders. Our study identified new risk loci, potential causal variants and genes for anxiety disorders, providing insights into the genetic architecture of anxiety disorders and potential therapeutic targets.
Identifiants
pubmed: 37945807
doi: 10.1038/s41562-023-01746-y
pii: 10.1038/s41562-023-01746-y
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : U2102205,31970561
Organisme : National Science Foundation of China | National Natural Science Foundation of China-Yunnan Joint Fund (NSFC-Yunnan Joint Fund)
ID : 202101AS070055
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Limited.
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