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

Background: Lifestyle is an important contributor of age-related chronic disease, but the association between lifestyle and the risk of idiopathic pulmonary fibrosis (IPF) remains unknown. The extent to which genetic susceptibility modifies the effects of lifestyle on IPF also remains unclear.

Research Question: Is there a joint effect or interaction of lifestyle and genetic susceptibility on the risk of developing IPF?

Study Design And Methods: This study included 407,615 participants from the UK Biobank study. A lifestyle score and a polygenic risk score were constructed separately for each participant. Participants were then classified into three lifestyle categories and three 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.

Results: With favorable lifestyle as the reference group, intermediate lifestyle (hazard ratio, 1.384; 95% CI, 1.218-1.574) and unfavorable lifestyle (hazard ratio, 2.271; 95% CI, 1.852-2.785) were significantly associated with an increased risk of IPF. For the combined effect of lifestyle and polygenic risk score, participants with unfavorable lifestyle and high genetic risk had the highest risk of IPF (hazard ratio, 7.796; 95% CI, 5.482-11.086) compared with those with favorable lifestyle and low genetic risk. Moreover, approximately 32.7% (95% CI, 11.3-54.1) of IPF risk could be attributed to the interaction of an unfavorable lifestyle and high genetic risk.

Interpretation: Exposure to unfavorable lifestyle significantly increased the risk of IPF, particularly in those with high genetic risk.