Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with a high burden of both pulmonary and extrapulmonary comorbidities.
Do these comorbidities have causal relationships with IPF?
We searched PubMed to pinpoint possible IPF-related comorbid conditions. Bidirectional Mendelian randomization (MR) was performed using summary statistics from the largest genome-wide association studies for these diseases to date in a two-sample setting. Findings were verified using multiple MR approaches under different model assumptions, replication datasets for IPF, and secondary phenotypes.
A total of 22 comorbidities with genetic data available were included. Bidirectional MR analyses showed convincing evidence for two comorbidities and suggestive evidence for four comorbidities. Gastroesophageal reflux disease, venous thromboembolism, and hypothyroidism were causally associated with an increased risk of IPF, while chronic obstructive pulmonary disease was causally associated with a decreased risk of IPF. For the reverse direction, IPF showed causal associations with a higher risk of lung cancer but a reduced risk of hypertension. Follow-up analyses of pulmonary function parameters and blood pressure measures supported the causal effect of chronic obstructive pulmonary disease on IPF and the causal effect of IPF on hypertension.
The present study suggests the causal associations between IPF and certain comorbidities from a genetic perspective. Further research is needed to understand the mechanisms of these associations.
Copyright © 2023. Published by Elsevier Inc.
