Gene discovery and biological insights into anxiety disorders from a large-scale multi-ancestry genome-wide association study.
Details
Serval ID
serval:BIB_EDBAC44C578C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Gene discovery and biological insights into anxiety disorders from a large-scale multi-ancestry genome-wide association study.
Journal
Nature genetics
ISSN
1546-1718 (Electronic)
ISSN-L
1061-4036
Publication state
Published
Issued date
10/2024
Peer-reviewed
Oui
Volume
56
Number
10
Pages
2036-2045
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Abstract
We leveraged information from more than 1.2 million participants, including 97,383 cases, to investigate the genetics of anxiety disorders across five continental groups. Through ancestry-specific and cross-ancestry genome-wide association studies, we identified 51 anxiety-associated loci, 39 of which were novel. In addition, polygenic risk scores derived from individuals of European descent were associated with anxiety in African, admixed American and East Asian groups. The heritability of anxiety was enriched for genes expressed in the limbic system, cerebral cortex, cerebellum, metencephalon, entorhinal cortex and brain stem. Transcriptome-wide and proteome-wide analyses highlighted 115 genes associated with anxiety through brain-specific and cross-tissue regulation. Anxiety also showed global and local genetic correlations with depression, schizophrenia and bipolar disorder and widespread pleiotropy with several physical health domains. Overall, this study expands our knowledge regarding the genetic risk and pathogenesis of anxiety disorders, highlighting the importance of investigating diverse populations and integrating multi-omics information.
Keywords
Genome-Wide Association Study, Humans, Anxiety Disorders/genetics, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Multifactorial Inheritance/genetics, Male, Bipolar Disorder/genetics, Transcriptome, Female, Schizophrenia/genetics, White People/genetics
Pubmed
Web of science
Create date
20/09/2024 14:43
Last modification date
05/11/2024 7:13