Large-scale sequencing identifies multiple genes and rare variants associated with Crohn's disease susceptibility.
Nat Genet
; 54(9): 1275-1283, 2022 09.
Article
in En
| MEDLINE
| ID: mdl-36038634
ABSTRACT
Genome-wide association studies (GWASs) have identified hundreds of loci associated with Crohn's disease (CD). However, as with all complex diseases, robust identification of the genes dysregulated by noncoding variants typically driving GWAS discoveries has been challenging. Here, to complement GWASs and better define actionable biological targets, we analyzed sequence data from more than 30,000 patients with CD and 80,000 population controls. We directly implicate ten genes in general onset CD for the first time to our knowledge via association to coding variation, four of which lie within established CD GWAS loci. In nine instances, a single coding variant is significantly associated, and in the tenth, ATG4C, we see additionally a significantly increased burden of very rare coding variants in CD cases. In addition to reiterating the central role of innate and adaptive immune cells as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Crohn Disease
Type of study:
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Nat Genet
Journal subject:
GENETICA MEDICA
Year:
2022
Document type:
Article
Affiliation country:
Reino Unido