Frailty and cardiometabolic diseases: a bidirectional Mendelian randomisation study.

• DOI: 10.1093/ageing/afac256
• Publication Date: 2022-11-02
• Authors: Jiahao Zhu; Dan Zhou; Jing Wang; Ye Yang; Dingwan Chen; Fan He; Yingjun Li
• Keywords: Mendelian Randomization; Stroke; Genome-wide Association Study; Genetic Association

Frailty is strongly associated with cardiometabolic diseases in observational studies. However, whether the observed association reflects causality requires clarification. We performed a bidirectional Mendelian randomisation (MR) study to assess causal relationship of frailty, measured by frailty index (FI), coronary artery disease (CAD), stroke and type 2 diabetes (T2D).We extracted summary genome-wide statistics for FI (N = 175,226), CAD (Ncase 60,801, Ncontrol 123,504), 40,585, 406,111) T2D 55,005, 400,308) among individuals European ancestry. Independent genetic variants each phenotype at significance level were taken as instruments. Two-sample MR analyses primarily conducted using inverse-variance-weighted method, followed various sensitivity validation analyses.Genetically predicted higher was significantly increased risk (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.17-1.96) (OR 1.80, CI 1.31-2.47) suggestively 1.36, 1.01-1.84). In reverse direction analysis, liability (beta 0.037, 0.019-0.055), 0.096, 0.051-0.141) 0.047, 0.036-0.059) showed significant associations FI. Results stable across analyses.Our strengthened evidence between diseases. Further understanding this will be critical optimisation care older adults.