Association of Genetic Instrumental Variables for Lung Function on Coronary Artery Disease Risk: A 2-Sample Mendelian Randomization Study

Abstract

Background: Lung function, assessed by forced expiratory volume in 1 second (FEV₁) and forced vital capacity (FVC), is inversely associated with coronary artery disease (CAD), but these associations could be because of confounding or reversed causality. We conducted a 2-sample Mendelian randomization study, using publicly available data from relevant genome-wide association studies, to examine the role of FEV₁ or FVC on CAD.

Methods: We used the most recent genome-wide association studies on lung function to extract genetic instruments related to FEV₁ and FVC (n=92 749). Data on the association between genetic instruments and CAD were obtained from Coronary Artery Disease Genome wide Replication and Meta-analysis plus The Coronary Artery Disease Genetics 1000 Genomes-based genome-wide association studies (60 801 CAD cases and 123 504 controls). We used inverse-variance weighting with a multiplicative random effect to estimate the genetic instrumented association of FEV₁ and FVC on CAD. Sensitivity analyses included weighted median and MR-Egger methods.

Results: Each SD greater FEV₁ was associated with a lower risk of CAD (odds ratio, 0.78 per SD; 95% confidence interval, 0.62-0.98) with a similar magnitude for FVC on CAD risk (odds ratio, 0.82 per SD; 95% confidence interval, 0.64-1.06). Estimates for FEV₁ were similar when using MR-Egger method (odds ratio, 0.80 per SD; 95% confidence interval, 0.33-1.94) although the magnitude was smaller for weighted median method (odds ratio, 0.93 per SD; 95% confidence interval, 0.75-1.17). Estimates for FVC in the sensitivity analyses were attenuated (median) or changed direction (MR-Egger).

Conclusions: Our study suggested an inverse relation between FEV₁ and CAD, but for FVC, evidence is less clear.

Keywords: Mendelian randomization analysis; coronary artery disease; forced expiratory volume; lung; odds ratio; vital capacity.