Identifying high-impact variants and genes in exomes of Ashkenazi Jewish inflammatory bowel disease patients.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
20 04 2023
20 04 2023
Historique:
received:
06
09
2021
accepted:
03
04
2023
medline:
24
4
2023
pubmed:
21
4
2023
entrez:
20
04
2023
Statut:
epublish
Résumé
Inflammatory bowel disease (IBD) is a group of chronic digestive tract inflammatory conditions whose genetic etiology is still poorly understood. The incidence of IBD is particularly high among Ashkenazi Jews. Here, we identify 8 novel and plausible IBD-causing genes from the exomes of 4453 genetically identified Ashkenazi Jewish IBD cases (1734) and controls (2719). Various biological pathway analyses are performed, along with bulk and single-cell RNA sequencing, to demonstrate the likely physiological relatedness of the novel genes to IBD. Importantly, we demonstrate that the rare and high impact genetic architecture of Ashkenazi Jewish adult IBD displays significant overlap with very early onset-IBD genetics. Moreover, by performing biobank phenome-wide analyses, we find that IBD genes have pleiotropic effects that involve other immune responses. Finally, we show that polygenic risk score analyses based on genome-wide high impact variants have high power to predict IBD susceptibility.
Identifiants
pubmed: 37080976
doi: 10.1038/s41467-023-37849-3
pii: 10.1038/s41467-023-37849-3
pmc: PMC10119186
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2256Subventions
Organisme : NIDDK NIH HHS
ID : U24 DK062429
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK123530
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK062422
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK062423
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK123758
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK062431
Pays : United States
Informations de copyright
© 2023. The Author(s).
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