Association between inflammatory bowel disease and frailty: a two-sample Mendelian randomization study

Abstract

Background: An association has been identified between inflammatory bowel disease (IBD) and frailty; however, the causal nature of this connection remains uncertain. We consequently conducted a two-sample Mendelian randomization (MR) analysis to explore this particular association.

Methods: We acquired distinct datasets for inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), and frailty from the published genome-wide association studies (GWAS) database, meticulously selecting instrumental variables (IVs). Subsequently, we employed a bidirection MR to examine the causal relationship between IBD (including CD and UC) and frailty. We utilized statistical methods, with a primary emphasis on inverse-variance weighted (IVW), accompanied by a series of sensitivity analyses to confirm heterogeneity and pleiotropy influenced the outcomes of the MR.

Results: We found positive causal effects of genetically increased frailty risk on IBD (OR: 1.015, 95% CI 1.005-1.025, P = 0.004). Furthermore, when scrutinizing specific IBD subtypes, both Crohn's disease (CD) and ulcerative colitis (UC) demonstrated an increased predisposition to frailty (OR: 1.018, 95% CI 1.01-1.027, P < 0.05) and (OR = 1.016, 95% CI 1.005-1.027, P < 0.05). Nevertheless, despite the consistent trends observed in the weighted median and MR-Egger regression analyses for both conditions, statistical significance remained elusive. Notably, the results of the inverse MR analysis did not establish an association between frailty and an elevated risk of IBD development.

Conclusions: Our research indicates that IBD, encompassing both CD and UC, may augment the propensity for frailty. Clinical practitioners must prioritize early frailty assessment in individuals afflicted with inflammatory bowel disease, inclusive of Crohn's disease and ulcerative colitis, facilitating proactive measures and timely interventions. However, our findings do not provide evidence supporting a causal effect of frailty on IBD (including CD and UC). Consequently, further studies are essential to explore the intricate mechanisms that clarify the effect of frailty on IBD.

Keywords: Causal relationship; Frailty; Genome-wide association studies; Inflammatory bowel disease; Mendelian randomization.