Cohort study finds increased risk of incident hypertension in adults with irritable bowel syndrome, highlighting shared genetic signals at the NCAM1 locus.
Key Points
To determine whether irritable bowel syndrome is associated with incident hypertension and to investigate potential underlying genetic and tissue-level mechanisms.
Analyzed 355,404 UK Biobank participants free of hypertension at baseline across a median follow-up of 14.09 years using multivariable Cox regression, propensity score matching, and sensitivity analyses.
Conducted bidirectional Mendelian randomization, Bayesian colocalization, and intestinal transcriptomic profiling to assess genetic susceptibility and tissue-level biological pathways.
Irritable bowel syndrome was associated with incident hypertension in multivariable Cox regression (HR, 1.26; 95% CI, 1.22–1.30) and after propensity score matching (HR, 1.22; 95% CI, 1.16–1.28).
Forward Mendelian randomization yielded a positive but imprecise primary inverse-variance weighted effect (OR, 1.18; 95% CI, 0.78–1.77) with positive associations in weighted median and outlier-corrected models, whereas reverse Mendelian randomization showed no association.
Bayesian colocalization identified shared signals for irritable bowel syndrome with diastolic (PP.H4, 0.903) and systolic blood pressure (PP.H4, 0.890) at the NCAM1 locus, where intestinal NCAM1 expression was decreased.