Genome-wide association study of right-sided colonic diverticulosis in a Korean population

Abstract

Diverticulosis results from complex interactions related to aging, environmental factors and genetic predisposition. Despite epidemiologic evidence of genetic risk factors, there has been no attempt to identify genes that confer susceptibility to colonic diverticulosis. We performed the first genome-wide association study (GWAS) on susceptibility to diverticulosis in a Korean population. A GWAS was carried out in 7,948 healthy individuals: 893 patients and 1,075 controls comprised the test set, and 346 patients and 305 controls comprised the replication set. Diverticulosis was diagnosed by colonoscopy during comprehensive medical check-ups, and single-nucleotide polymorphisms (SNPs) related to diverticulosis were detected with the Affymetrix Axiom KORV1.1-96 Array. In all, 9 SNPs were identified in three SNP aggregates in the test set (P < 10 −3 , within 200 kb) after adjusting for sex. All the SNPs were replicated in the replication set (P < 0.05). Three SNPs were near the WNT4 gene, four near the RHOU gene, and two in the OAS1/3 genes. The top SNP associated with right-sided colonic diverticulosis was rs22538787, located near the WNT4 gene [combined set, P-value = 3.128 × 10 −6 , odds ratio = 1.415 (95% confidence interval: 1.223–1.637)]. These 9 novel SNP alleles associated with the WNT4, RHOU, and OAS1/3 genes are possibly involved in the underlying genetic susceptibility to right-sided diverticulosis. Our results provide basic knowledge about the development of diverticulosis in an Asian population.

Age, alcohol, sex, and metabolic factors as risk factors for colonic diverticulosis

“…This difference may be due to the genetic predispositions of the subjects. Choe et al [ 17 ] performed a genome-wide association study in South Korea and found that the WNT 4, RHOU , and OAS 1/3 genes might be the underlying cause of the development of right-sided diverticulosis.…”

Dietary pattern and its association with right‐colonic diverticulosis

“…There must be genetic and environmental reasons. A recent genome‐wide association study among Koreans have discovered that several single‐nucleotide polymorphisms are associated with right‐colonic diverticulosis 34 . Meanwhile, an observational study of Japanese‐Americans living in Hawaii showed higher incidence of diverticulosis compared with the Japanese living in Japan; however, they still maintained the right‐side predominance 35 .…”

Pathophysiology of Diverticular Disease: From Diverticula Formation to Symptom Generation

“…This study was carried out on 893 patients with right-sided diverticulosis or bilateral, and 1075 controls, and replicated on 346 patients and 305 controls. Although this study has a statistical limitation, as the Bonferroni correction deleted the statistical significance, it highlighted 9 SNPs located in 3 new candidate genes: WNT4 , RHOU, and OAS1/3 [ 39 ]. Both the WNT4 and the RHOU genes encode for members of the WNT signaling pathway.…”

“…Moreover, the WNT signaling is associated with intestinal glial and neuronal differentiation in rats, together with anti-inflammatory activity in the enteric nervous system (ENS) [ 42 ]. Differently, the members of the OAS family are protein induced by interferon and linked to antiviral and apoptotic responses [ 43 ], strengthening the idea of chronic low-grade inflammation in DD pathophysiology [ 39 ].…”