Whole-exome sequencing in UK Biobank reveals rare genetic architecture for depression.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
26 Feb 2024
26 Feb 2024
Historique:
received:
02
11
2023
accepted:
02
02
2024
medline:
27
2
2024
pubmed:
27
2
2024
entrez:
26
2
2024
Statut:
epublish
Résumé
Nearly two hundred common-variant depression risk loci have been identified by genome-wide association studies (GWAS). However, the impact of rare coding variants on depression remains poorly understood. Here, we present whole-exome sequencing analyses of depression with seven different definitions based on survey, questionnaire, and electronic health records in 320,356 UK Biobank participants. We showed that the burden of rare damaging coding variants in loss-of-function intolerant genes is significantly associated with risk of depression with various definitions. We compared the rare and common genetic architecture across depression definitions by genetic correlation and showed different genetic relationships between definitions across common and rare variants. In addition, we demonstrated that the effects of rare damaging coding variant burden and polygenic risk score on depression risk are additive. The gene set burden analyses revealed overlapping rare genetic variant components with developmental disorder, autism, and schizophrenia. Our study provides insights into the contribution of rare coding variants, separately and in conjunction with common variants, on depression with various definitions and their genetic relationships with neurodevelopmental disorders.
Identifiants
pubmed: 38409228
doi: 10.1038/s41467-024-45774-2
pii: 10.1038/s41467-024-45774-2
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1755Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
ID : R01MH118233
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
ID : R01MH117646
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
ID : R01MH118233
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
ID : R01MH118233
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
ID : R01MH118233
Informations de copyright
© 2024. The Author(s).
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