한빛사논문
- 조회853
The University of North Carolina at Chapel Hill (UNC)
Jungkyun Seo 1, Hongwei Liu 2, Kristin Young 1, Xinruo Zhang 1, Temitope O Keku 3, Corbin D Jones 4, Kari E North 1, Robert S Sandler 5, Anne F Peery 6 *
1Department of Epidemiology, The University of North Carolina, Chapel Hill, North Carolina, USA.
2Department of Genetics, The University of North Carolina, Chapel Hill, North Carolina, USA.
3Center for Gastrointestinal Biology and Disease, The University of North Carolina, Chapel Hill, North Carolina, USA.
4Department of Biology and Integrative Program for Biological and Genome Sciences, The University of North Carolina, Chapel Hill, North Carolina, USA.
5Gastroenterology and Hepatology, The University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
6Center for Gastrointestinal Biology and Disease, The University of North Carolina, Chapel Hill, North Carolina, USA.
*Corresponding author: correspondence to Anne F Peery
Abstract
Objective Colonic diverticulosis is a prevalent condition among older adults, marked by the presence of thin-walled pockets in the colon wall that can become inflamed, infected, haemorrhage or rupture. We present a case–control genetic and transcriptomic study aimed at identifying the genetic and cellular determinants underlying this condition and the relationship with other gastrointestinal disorders.
Design We conducted DNA and RNA sequencing on colonic tissue from 404 patients with (N=172) and without (N=232) diverticulosis. We investigated variation in the transcriptome associated with diverticulosis and further integrated this variation with single-cell RNA-seq data from the human intestine. We also integrated our expression quantitative trait loci with genome-wide association study using Mendelian randomisation (MR). Furthermore, a Polygenic Risk Score analysis gauged associations between diverticulosis severity and other gastrointestinal disorders.
Results We discerned 38 genes with differential expression and 17 with varied transcript usage linked to diverticulosis, indicating tissue remodelling as a primary diverticula formation mechanism. Diverticula formation was primarily 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 CCN3, CRISPLD2, ENTPD7, PHGR1 and TNFSF13, with potential causal effects on diverticulosis. Notably, ENTPD7 upregulation was confirmed in diverticulosis cases. Additionally, diverticulosis severity was positively correlated with genetic predisposition to diverticulitis.
Conclusion Our results suggest that tissue remodelling is a primary mechanism for diverticula formation. Individuals with an increased genetic proclivity to diverticulitis exhibit a larger numbers of diverticula on colonoscopy.
논문정보
- Research article
- 2024년 03월 (BRIC 등록일 2024-03-12)
- 국외 연구진
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