Abstract
BackgroundGenome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with diseases of the colon including inflammatory bowel diseases (IBD) and colorectal cancer (CRC). However, the functional role of many of these SNPs is largely unknown and tissue-specific resources are lacking. Expression quantitative trait loci (eQTL) mapping identifies target genes of disease-associated SNPs. This study provides a comprehensive eQTL map of distal colonic samples obtained from 40 healthy African Americans and demonstrates their relevance for GWAS of colonic diseases.Results8.4 million imputed SNPs were tested for their associations with 16,252 expression probes representing 12,363 unique genes. 1,941 significant cis-eQTL, corresponding to 122 independent signals, were identified at a false discovery rate (FDR) of 0.01. Overall, among colon cis-eQTL, there was significant enrichment for GWAS variants for IBD (Crohn’s disease [CD] and ulcerative colitis [UC]) and CRC as well as type 2 diabetes and body mass index. ERAP2, ADCY3, INPP5E, UBA7, SFMBT1, NXPE1 and REXO2 were identified as target genes for IBD-associated variants. The CRC-associated eQTL rs3802842 was associated with the expression of C11orf93 (COLCA2). Enrichment of colon eQTL near transcription start sites and for active histone marks was demonstrated, and eQTL with high population differentiation were identified.ConclusionsThrough the comprehensive study of eQTL in the human colon, this study identified novel target genes for IBD- and CRC-associated genetic variants. Moreover, bioinformatic characterization of colon eQTL provides a tissue-specific tool to improve understanding of biological differences in diseases between different ethnic groups.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1292-z) contains supplementary material, which is available to authorized users.
Highlights
Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with diseases of the colon including inflammatory bowel diseases (IBD) and colorectal cancer (CRC)
The analysis showing the enrichment of colon Expression quantitative trait loci (eQTL) among SNPs associated with colonic diseases supported the usefulness of colon eQTL as a tissue-specific tool to improve 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
Summary
Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with diseases of the colon including inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Genome-wide association studies (GWAS), conducted primarily in populations of European descent, have identified single nucleotide polymorphisms (SNPs) associated with IBD, including both ulcerative colitis (UC) [1,2,3,4,5,6] and Crohn’s disease (CD) [7,8,9,10,11,12,13,14,15,16,17,18,19], as well as CRC [20,21,22,23,24,25,26,27,28,29,30]. Expression quantitative trait loci (eQTL) mapping associates genome-wide SNPs with mRNA expression from the same individuals in a particular tissue to
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