Immunochip meta-analysis in European and Argentinian populations identifies two novel genetic loci associated with celiac disease.
Isis Ricaño-PonceJavier Gutierrez-AchuryAna Florencia CostaPatrick DeelenAlexander KurilshikovMaria Magdalena ZorroMathieu PlatteelAdriaan van der Graafnull nullSerena SannaOscar DaffraAlexandra ZhernakovaJingyuan FuGosia TrynkaEdgardo SmecuolSonia Isabel NiveloniJulio Cesar BaiVinod KumarCisca WijmengaPublished in: European journal of human genetics : EJHG (2019)
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.
Keyphrases
- genome wide
- celiac disease
- dna methylation
- signaling pathway
- copy number
- systematic review
- rheumatoid arthritis
- pi k akt
- poor prognosis
- genome wide association study
- emergency department
- gene expression
- epithelial mesenchymal transition
- induced apoptosis
- genome wide identification
- risk assessment
- genetic diversity
- long non coding rna
- protein kinase