Genetic Effects on Transcriptome Profiles in Colon Epithelium Provide Functional Insights for Genetic Risk Loci.

摘要: Background & Aims The association of genetic variation with tissue-specific gene expression and alternative splicing guides functional characterization complex trait-associated loci may suggest novel genes implicated in disease. Here, our aims were as follows: (1) to generate reference profiles colon mucosa compare them across subsites (ascending, transverse, descending), (2) identify quantitative trait (QTLs), (3) find traits for which identified QTLs contribute single-nucleotide polymorphism (SNP)-based heritability, (4) propose candidate effector genes, (5) provide a web-based visualization resource. Methods We collected colonic mucosal biopsy specimens from 485 healthy adults performed bulk RNA sequencing. genome-wide SNP genotyping blood leukocytes. Statistical approaches bioinformatics software were used QTL identification downstream analyses. Results provided complete quantification described their differences. thousands defined enrichment at regulatory regions. found that part the SNP-based heritability diseases affecting tissue, such colorectal cancer inflammatory bowel disease, but also other tissues, psychiatric conditions, can be explained by QTLs. multiple phenotypes. Finally, we Colon Transcriptome Explorer web application. Conclusions large subsites. Our findings greater etiologic insight into influenced transcriptomic changes tissue.