Immunochip meta-analysis in European and Argentinian populations identifies two novel genetic loci associated with celiac disease.
Eur J Hum Genet
; 28(3): 313-323, 2020 03.
Article
in En
| MEDLINE
| ID: mdl-31591516
ABSTRACT
Celiac disease (CeD) is a common immune-mediated disease of the small intestine that is triggered by exposure to dietary gluten. While the HLA locus plays a major role in disease susceptibility, 39 non-HLA loci were also identified in a study of 24,269 individuals. We now build on this earlier study by adding 4125 additional Caucasian samples including an Argentinian cohort. In doing so, we not only confirm the previous associations, we also identify two novel independent genome-wide significant associations at loci 12p13.31 and 22q13.1. By applying a genomics approach and differential expression analysis in CeD intestinal biopsies, we prioritize potential causal genes at these novel loci, including LTBR, CYTH4, and RAC2. Nineteen prioritized causal genes are overlapping known drug targets. Pathway enrichment analysis and expression of these genes in CeD biopsies suggest that they have roles in regulating multiple pathways such as the tumor necrosis factor (TNF) mediated signaling pathway and positive regulation of I-κB kinase/NF-κB signaling.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Celiac Disease
/
Polymorphism, Single Nucleotide
/
Genetic Loci
Type of study:
Prognostic_studies
/
Risk_factors_studies
/
Systematic_reviews
Limits:
Humans
Country/Region as subject:
America do sul
/
Argentina
/
Europa
Language:
En
Journal:
Eur J Hum Genet
Journal subject:
GENETICA MEDICA
Year:
2020
Document type:
Article
Affiliation country: