Genetic liability to gastro-esophageal reflux disease, obesity, and risk of idiopathic pulmonary fibrosis

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 instru-ment 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. (c) 2023 [The Author/The Authors] Published by Elsevier B.V. on behalf of The Japanese Respiratory Society. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

Automated summary

In this study, multivariable Mendelian randomization was used to examine the causal relationship between gastro-esophageal reflux disease (GORD) and idiopathic pulmonary fibrosis (IPF) after adjusting for BMI. The results showed that although genetic liability to GORD increased the risk of IPF, this relationship was attenuated after adjusting for BMI. Therefore, intervention for GORD alone is unlikely to reduce the risk of IPF, while reducing obesity may be a better approach.