Causal Relationship between Frailty and Chronic Obstructive Pulmonary Disease or Asthma: a two sample bidirectional Mendelian Randomization Study

Observational studies have established a strong association between frailty and obstructive lung diseases. However, the causal nature of this association remains unclear. To address this gap, we conducted a bidirectional Mendelian randomization (MR) study to investigate the causal relationship between frailty, as measured by the frailty index (FI), and chronic obstructive pulmonary disease (COPD) or asthma. The latest meta-analysis of genome-wide association studies for FI, which included individuals of European ancestry from UK Biobank and TwinGene (N = 175,226), yielded the genetic instruments for frailty and outcome summary statistics. The genetic instrument for COPD and asthma, as well as the outcome summary data, were derived from the GWAS conducted on individuals of European ancestry from the FinnGen, with a sample size of 16,410 cases and 283,589 controls for COPD, and 37,253 cases and 187,112 controls for asthma. The analysis of MR was conducted employing the inverse-variance weighted (IVW) method, complemented by the weighted median method, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO) test. Our results showed that genetically predicted higher FI was significantly associated with increased risk of COPD (odds ratio [OR] 1.75, 95% confidence interval [CI] 1.29–2.36) and asthma (OR 2.10, 95% CI 1.44–3.16). In the reverse direction analysis, genetic liability to both COPD (beta 0.06, 95% CI 0.01–0.10) and asthma (beta 0.08, 95% CI 0.06–0.11) showed significant associations with a higher FI. Our research has reinforced the existing evidence supporting a reciprocal causal relationship between frailty and obstructive lung diseases. A deeper comprehension of this interconnection is imperative for the prevention and treatment of obstructive lung diseases.