Genetic liability to gastro-esophageal reflux disease, obesity, and risk of idiopathic pulmonary fibrosis
Caroline Cotton, Philip Alton, David M. Hughes, Sizheng Steven Zhao
Abstract
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.