Understanding the link between regulatory RNA regions and genomic variation in coeliac disease.

Abstract

Coeliac disease (CD) is a chronic immune-mediated inflammatory disorder triggered by dietary gluten ingestion in genetically predisposed individuals. While gluten-specific T cells and HLA-DQ2/DQ8 alleles are critical to the disease onset, they account for less than half of the genetic heritability, underscoring the complexity of CD's genetic underpinnings. Genome-Wide Association Studies (GWAS) and next-generation sequencing have identified 42 non-HLA loci associated with CD risk, yet the molecular mechanisms underlying these associations remain largely unexplored. Notably, most disease-associated single nucleotide polymorphisms (SNPs) associated with CD are located in non-coding genomic regions, highlighting the regulatory potential of these variants. Emerging evidence demonstrates that non-coding RNAs (ncRNAs), particularly microRNAs and long non-coding RNAs, play crucial roles in gene regulation and disease development. Recent advances in transcriptomics have revealed new transcribed regions of the genome, shedding light on the functional significance of previously unannotated sequences. This review discusses the contribution of non-coding SNPs located in regulatory RNA regions to CD development, emphasizing the role of long non-coding RNAs and their potential as therapeutic targets.