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.
Highlights
Colonic diverticulosis is an anatomical alteration characterized by the presence of a hernial sac protruding through a weak area of the intestinal muscle[1]
Since the majority of Korean populations are ethnically homogenous[16] and the Korean population included in our study showed a distinct clustering in the PCA plot, we did not adjust for principal component scores
Diverticulosis is a disease resulting from complex interactions among the aging process, multiple environmental factors such as diet and lifestyle, and genetic predisposition[9]
Summary
Colonic diverticulosis is an anatomical alteration characterized by the presence of a hernial sac protruding through a weak area of the intestinal muscle[1]. Recent epidemiologic data suggest that genetic factors contribute considerably to the occurrence of diverticulosis[8,9]. Recent large twin studies have provided conclusive evidence that genetic factors contribute to the occurrence of diverticulosis and have found that genetic predisposition accounts for approximately 40% to 50% of diverticulosis[8,10,11]. Connection between these inherited syndromes and diverticulosis provides strong evidence of a genetic predisposition for diverticulosis and might offer information about its pathogenesis. Despite this plausible epidemiologic evidence of genetic risk factors, there has been no attempt made to identity genes that confer susceptibility to colonic diverticulosis. The aim of this study was to identify single-nucleotide polymorphisms (SNPs) that could cause right-sided diverticulosis in a Korean population
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