A comprehensive genome-wide association study has identified genetic links between irritable bowel syndrome (IBS) and cardiovascular disease.
In the study, published in Cellular and Molecular Gastroenterology and Hepatology, investigators recruited 24,735 patients with IBS 77,149 asymptomatic controls from the UK Biobank and Lifelines cohorts. IBS was classified according to the Rome III criteria, focusing on single-nucleotide polymorphism (SNP)-based heritability (h2SNP) and genetic correlations (rg) with other traits. The prevalence rates were as follows: IBS-mixed subtype (IBS-M) at 13.4%, IBS diarrhea-predominant subtype (IBS-D) at 12.4%, and IBS constipation-predominant subtype (IBS-C) at 11.7%.
IBS defined by Rome III criteria exhibited an SNP-heritability of up to 13%, indicating a genetic component. The investigators identified genetic correlations between IBS and cardiovascular diseases such as coronary artery disease and hypertension (rg = 0.20–0.45). Additionally, four independent genome-wide association study signals were detected, including two novel loci for IBS (rs2035380) and IBS-M (rs2048419). These loci have previously been associated with hypertension and coronary artery disease. Functional annotation of these loci highlighted genes involved in circadian rhythm (BMAL1), intestinal barrier function (CLDN23), immunomodulation (MFHAS1), and the cyclic adenosine monophosphate pathway (ADCY2).
Patients with IBS exhibited a higher number of comorbidities compared to control subjects (P ≤ 5.1×10^–161). Significant associations were observed with gastrointestinal and psychiatric disorders (odds ratio [OR] = 2.0–2.7, P ≤ 7.7×10^–39). Additionally, there were notable links to other anxiety disorders (OR = 3.3–3.9, P ≤ 4.5×10^–26) and dyspepsia (OR = 2.9–3.8, P ≤ 1.0×10^–44). Essential hypertension was found to be associated with all IBS subtypes (OR = 1.4–1.6, P ≤ 1.3×10^–12). For patients with IBS-C, there was an association with angina pectoris (OR = 2.2, P = 1.2×10^–15) and chronic ischemic heart disease (OR = 1.8, P = 2.1×10^–11).
Full disclosures can be found in the published study.