RESUMEN
BACKGROUND: Gastro-esophageal reflux disease (GORD) has been associated with a greater risk of idiopathic pulmonary fibrosis (IPF) in observational studies, but results are limited by confounding. We used multivariable Mendelian randomization to examine their causal relationship, adjusting for BMI. METHODS: We selected genetic instruments for GORD from genome-wide association studies of 80,265 cases and 305,011 controls. Genetic association data for IPF were obtained from 2668 cases and 8591 controls, and BMI from 694,649 individuals. We used the inverse-variance weighted method and a series of sensitivity analyses including weak instrument robust methods. RESULTS: Although genetic liability to GORD increased IPF risk (OR 1.58; 95% CI 1.10-2.25), this result was attenuated to include the null after adjusting for BMI (OR 1.14; 95% CI 0.85-1.52). CONCLUSION: Intervention for GORD alone is unlikely to reduce the risk of IPF, whereas reducing obesity may be a better approach.
Asunto(s)
Reflujo Gastroesofágico , Fibrosis Pulmonar Idiopática , Humanos , Estudio de Asociación del Genoma Completo , Reflujo Gastroesofágico/complicaciones , Fibrosis Pulmonar Idiopática/epidemiología , Fibrosis Pulmonar Idiopática/genética , Fibrosis Pulmonar Idiopática/complicaciones , Obesidad/genética , Obesidad/complicaciones , Polimorfismo de Nucleótido SimpleRESUMEN
Interleukin-5 (IL-5) inhibitors have revolutionized the management of eosinophilic asthma. However, IL-5 is thought to play a protective role in atherosclerosis, and cardiovascular safety data for IL-5i are scarce. We used population-level data to examine the association between genetically proxied IL-5i and the risk of cardiovascular diseases. Genetic instruments for IL-5i were selected from a genome-wide association study of eosinophil count in 563,946 individuals. Genetic association data for coronary artery disease were obtained from 60,801 cases, 40,585 stroke cases, 7988 venous thromboembolism cases, and up to 406,111 controls. We used the inverse-variance weighted method and a series of sensitivity analyses. Nine genetic variants were selected to instrument IL-5i. Genetically proxied IL-5i was not associated with the risk of coronary heart disease (OR 0.82, 95%CI 0.65-1.03), stroke (OR 1.10; 0.95-1.27), or venous thromboembolism (OR 0.87; 0.64-1.17). We found no genetic evidence to suggest that IL-5i affects the risk of adverse cardiovascular and thromboembolic events.