Characterization of expression quantitative trait loci in the human colon

Area of Science:

• Genomics
• Molecular Biology
• Human Genetics

Background:

• Identifying causal genes for genetic risk loci in inflammatory bowel disease (IBD) and colorectal cancer (CRC) is challenging.
• Expression quantitative trait loci (eQTL) studies link genetic variants to gene expression, aiding gene prioritization.
• Existing eQTL datasets lack crucial tissue-specific data from primary gastrointestinal tissues.

Purpose of the Study:

• To discover novel expression quantitative trait loci (eQTLs) in the human terminal ileum and colon.
• To generate a catalog of tissue-specific eQTLs for the gastrointestinal tract.
• To investigate the role of eQTLs in genetic risk loci for IBD and CRC.

Main Methods:

• Conducted a genome-wide cis-eQTL analysis on >3,600,000 variants and 13,558 probes.
• Utilized endoscopic tissue samples from the terminal ileum and four colonic locations.
• Included 65 controls and patients with quiescent IBD.

Main Results:

• Identified 1312 independent eQTLs for 1222 genes in rectal mucosa, with significant numbers in other colonic sections and the terminal ileum.
• Found that 26% of rectal eQTL-associated genes were novel compared to existing datasets.
• Discovered 11 IBD risk loci tag single-nucleotide polymorphisms (SNPs) that were also rectal eQTLs, including a CRC locus eQTL for COLCA2.

Conclusions:

• Generated a comprehensive catalog of ileal and colonic eQTLs.
• Confirmed the significant tissue specificity of eQTLs.
• Demonstrated the utility of tissue-specific eQTLs in fine-mapping genetic risk loci for gastrointestinal diseases.