The impact of obesity on lung function measurements and respiratory disease: A Mendelian randomization study

Abstract Introduction Observational studies have shown that body mass index (BMI) and waist‐to‐hip ratio (WHR) are both inversely associated with lung function, as assessed by forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). However, observational data are susceptible to confounding and reverse causation. Methods We selected genetic instruments based on their relevant large‐scale genome‐wide association studies. Summary statistics of lung function and asthma came from the UK Biobank and SpiroMeta Consortium meta‐analysis ( n = 400,102). After examining pleiotropy and removing outliers, we applied inverse‐variance weighting to estimate the causal association of BMI and BMI‐adjusted WHR (WHRadjBMI) with FVC, FEV1, FEV1/FVC, and asthma. Sensitivity analyses were performed using weighted median, MR‐Egger, and MRlap methods. Results We found that BMI was inversely associated with FVC (effect estimate, −0.167; 95% confidence interval (CI), −0.203 to −0.130) and FEV1 (effect estimate, −0.111; 95%CI, −0.149 to −0.074). Higher BMI was associated with higher FEV1/FVC (effect estimate, 0.079; 95%CI, 0.049 to 0.110) but was not significantly associated with asthma. WHRadjBMI was inversely associated with FVC (effect estimate, −0.132; 95%CI, −0.180 to −0.084) but has no significant association with FEV1. Higher WHR was associated with higher FEV1/FVC (effect estimate, 0.181; 95%CI, 0.130 to 0.232) and with increased risk of asthma (effect estimate, 0.027; 95%CI, 0.001 to 0.053). Conclusion We found significant evidence that increased BMI is suggested to be causally related to decreased FVC and FEV1, and increased BMI‐adjusted WHR could lead to lower FVC value and higher risk of asthma. Higher BMI and BMI‐adjusted WHR were suggested to be causally associated with higher FEV1/FVC.