Association of Genetic Instrumental Variables for Lung Function on Coronary Artery Disease Risk: A 2-Sample Mendelian Randomization Study. (April 2018)

• Record Type: Journal Article
• Authors: Au Yeung, Shiu Lun; Borges, Maria-Carolina; Lawlor, Debbie A.
• Is Part Of: Circulation. Volume 11:Number 4(2018)
• Publication Date: 2018-04
• Subjects: coronary artery disease -- forced expiratory volume -- lung -- Mendelian randomization analysis -- odds ratio -- vital capacity; Cardiovascular system -- Diseases -- Periodicals; Cardiovascular system -- Genetics -- Periodicals; Cardiovascular Diseases -- genetics; Precision Medicine; Periodical; Fulltext; Internet Resources; Periodicals; Electronic journals; Periodicals; 616.1042
• DOI: 10.1161/CIRCGEN.117.001952
• Languages: English
• ISSNs: 2574-8300

Abstract

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. Abstract : Supplemental Digital Content is available in the text.