Lung function and the risk of frailty in the European population: a mendelian randomization study

Epidemiological evidence has suggested a relationship between lung function and frailty, but the precise nature of the causality remains unclear. In this study, we applied a two-sample Mendelian randomization (MR) analysis to determine the causal effects of lung function on frailty. Single nucleotide polymorphisms (SNPs) independently related (P ≤ 5E-08) to lung function, as identified by genome-wide association study (GWAS), were applied as instrumental variables (IV). The association with frailty index (FI) was investigated using summary-level data from the latest GWAS on FI (n = 175,226). Different statistical methods were employed to evaluate the causal estimates between lung function and FI. The pleiotropy, heterogeneity, and leave-one-out analysis were applied to confirm the stability of the MR estimates. Using the random-effect inverse-variance weighted approach, genetically proxied forced expiratory volume in the first second (FEV1), ratio of FEV1 on forced vital capacity (FVC) [FEV1/FVC], and peak expiratory flow (PEF) were significantly and inversely associated with FI (FEV1, β = -0.08, P = 2.03E-05; FEV1/FVC, β = -0.06, P = 9.51E-06; PEF, β = -0.07, P = 4.09E-04) with good statistical power (99.7-100%). However, no significant association was observed between FVC and FI (β = -0.01, P = 0.681). Leave-one-out analysis showed that there was no single SNP driving the bias of the estimates. There was potential heterogeneity, but no obvious pleiotropy was founded in this MR study. Our findings indicate that impaired pulmonary function is closely related to the risk of frailty. Enhancing lung function in the elderly population may contribute to the prevention of frailty to a certain extent.