Association between Crohn's disease and frailty: a bidirectional Mendelian randomization study / 预防医学

ABSTRACT

Objective @#o evaluate the association between Crohn's disease (CD) and frailty using a Mendelian randomization (MR) approach, so as to provide the evidence for prevention and control strategies.@*Methods@#Genetic association data for CD were collected through the International Inflammatory Bowel Disease Genetics Consortium, with 20 883 samples and 12 276 506 single nucleotide polymorphism (SNP), and genetic association data for frailty were collected through a meta-analysis including 175 226 samples and 7 589 717 SNPs. A forward MR analysis was performed using the inverse-variance weighted (IVW) method with 37 CD-associated SNPs as instrumental variables, and frailty as the study outcome, and a reverse MR analysis was performed with 13 frailty-associated SNPs as instrumental variables and CD as the study outcome. The heterogeneity was assessed using the Cochran's Q test, and the horizontal pleiotropy was assessed using the MR-PRESSO global test and MR-Egger regression. In addition, the robustness of the results was verified with the leave-one-out. @*Results@#Forward MR analysis results showed that patients with genetically predicted CD had an increased risk of frailty index relative to those without CD (β=0.018, 95%CI 0.011-0.026, P<0.05). Cochran's Q test detected no heterogeneity (P>0.05), and neither the MR-PRESSO test nor the MR-Egger regression revealed horizontal pleiotropy of instrumental variables (both P>0.05). Leave-one-out analysis showed robustness of the MR analysis results. Reverse MR analysis showed no association between frailty index and the risk of CD (OR=0.740, 95%CI 0.206-2.661, P>0.05). @*Conclusions@#Genetically predicted CD is associated with an increased risk of frailty. It is suggested that screening and prevention of frailty should be reinforced among CD patients.