Lifestyle, Genetic Susceptibility, and the Risk of Idiopathic Pulmonary Fibrosis: A Large Prospective Cohort Study

Abstract

Lifestyle is thought to be an important contributor of age-related chronic disease, but the association between lifestyle and the risk of idiopathic pulmonary fibrosis (IPF) remains unknown. Also, the extent to which genetic susceptibility modifies the effects of lifestyle on IPF remains unclear. Whether there is joint effect or interaction of lifestyle and genetic susceptibility on the risk of developing IPF? Our study included 407615 participants from the UK Biobank. We constructed a lifestyle score and a polygenic risk score (PRS) for each participant, separately. Participants were then classified into 3 lifestyle categories and 3 genetic risk categories based on the corresponding score. Cox models were fitted to assess the association of lifestyle and genetic risk with the risk of incident IPF. With favorable lifestyle as the reference group, intermediate lifestyle (hazard ratio (HR): 1.384, 95% confidence interval (CI): 1.218-1.574) and unfavorable lifestyle (HR: 2.271, 95% CI: 1.852-2.785) were significantly associated with increased risk of IPF. For the combined effect of lifestyle and PRS, participants with unfavorable lifestyle and high genetic risk had the highest risk of IPF (HR: 7.796, 95% CI: 5.482-11.086) compared to those with favorable lifestyle and low genetic risk. Moreover, approximately 32.7% (11.3%, 54.1%) of IPF risk could be attributed to the interaction of an unfavorable lifestyle and high genetic risk. Exposure to unfavorable lifestyle significantly increased the risk of IPF, particularly in those with high genetic risk.