In a recent study published in the journal BMC Genomics, researchers from Chicago were able to identify new genetic variants in inflammatory bowel disease and colorectal cancer risk. The research team determined that bioinformatic characterization of the colon provides a tissue-specific tool to improve understanding of biological differences in diseases between different ethnic groups.
Genetic susceptibility is thought to play a role in common diseases, including those affecting the colon such as inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Genome-wide association studies (GWAS), have identified single nucleotide polymorphisms (SNPs) associated with IBD, including both ulcerative colitis (UC) and CRC. Expression quantitative trait loci (eQTL) mapping associates genome-wide SNPs with mRNA expression from the same individuals in a particular tissue to identify regulatory variation.
Importantly, it has been shown that variants identified by GWAS as being reproducibly associated with complex traits are enriched for eQTL in various cell types. However, comprehensive genome-wide eQTL mapping has not previously been performed in the human colon, which is the relevant tissue for colonic diseases like IBD and CRC.
To address this lack of knowledge, in the study entitled “Enrichment of inflammatory bowel disease and colorectal cancer risk variants in colon expression quantitative trait loci,” Imge Hulur from the Department of Medicine in Chicago and colleagues conducted a comprehensive eQTL map of distal colonic samples obtained from 40 healthy African Americans and demonstrates their relevance for GWAS of colonic diseases.
The research team analyzed a total of 8.4 million imputed SNPs for their associations with 16,252 expression probes, representing 12,363 unique genes. The analysis showed that the enrichment of colon eQTL among SNPs was associated with colonic diseases, supporting the usefulness of colon eQTL as a tissue-specific tool for improving the understanding of colonic disease susceptibility.
The utility of colon eQTL for studying the genetic basis of inter-ethnic differences in colonic disease risk was demonstrated by showing their enrichment for SNPs that exhibit high allele frequency differences between European and African populations. The researchers indicate that these SNPs could mediate population specific gene expression responses, which could translate into differences in disease risk.
These findings offer novel insights into the functional basis of genetic susceptibility for colonic inflammatory and malignant diseases, and provides a tissue-specific resource for future studies.
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