Diverticulosis, Colonic study with RNA-Seq, SNP/CNV Genotypes (NGS) data on dbGaP (404 participants)

phs003556 — Risk Factors for Asymptomatic Diverticulosis

<p>Data for this analysis came from a prospective study of colonic diverticulosis at the University of North Carolina Hospital in Chapel Hill, North Carolina (NIH R01DK094738). This is a case-control genetic and transcriptomic study to identify the genetic and cellular determinants underlying colonic diverticulosis and the relationship with other gastrointestinal disorders. The study inclusion and exclusion are described below. DNA and RNA sequencing were performed on colonic tissue from 404 patients with (N=172) and without (N=232) diverticulosis. We assessed variation in the transcriptome associated with diverticulosis and integrated this variation with human intestine single-cell RNA-seq data. We integrated our expression quantitative trait loci with GWAS using Mendelian Randomization. A polygenic risk score analysis examined associations between severity of diverticulosis and other gastrointestinal disorders. We identified 38 genes with differential expression and 17 genes with varied transcript usage linked to diverticulosis. Our results suggest tissue remodeling as a primary mechanism for diverticula formation. The presence of diverticulosis was linked to stromal and epithelial cells in the colon including endothelial cells, myofibroblasts, fibroblasts, goblet, tuft, enterocytes, neurons, and glia. MR highlighted five genes including <a href="https://www.ncbi.nlm.nih.gov/gene/4856">CCN3</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/83716">CRISPLD2</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/57089">ENTPD7</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/644844">PHGR1</a>, and <a href="https://www.ncbi.nlm.nih.gov/gene/8741">TNFSF13</a>. In diverticulosis cases, ENTPD7 upregulation was confirmed. A greater burden of diverticula was positively correlated with genetic predisposition to diverticulitis. The data related to the study including total RNA-Seq, SNP array and imputed genotypes will be available through dbGaP.</p>