Unraveling the Complex Relationship Between Gastroesophageal Reflux Disease, Lifestyle Factors, and Interstitial Lung Disease: Insights From Two-Sample Mendelian Randomization Analyses.

Background Although the cause of interstitial lung disease (ILD) remains uncertain, it is believed to be a combination of genetic and non-inherited factors, such as smoking and diet. This research aims to evaluate the impact of gastroesophageal reflux disease (GERD) and other modifiable risk factors on the likelihood of developing ILD by utilizing two-sample Mendelian randomization. Methodology The research utilized publicly accessible single-nucleotide polymorphisms (SNPs) that were deemed significant on a genome-wide scale. These SNPs were chosen from prior studies conducted by various consortia. The study examined GERD and a wide range of smoking habits, including the age at which individuals started smoking, the intensity of their smoking, and whether their mothers smoked. Additionally, the study considered other relevant risk factors such as key dietary factors, coffee consumption, body mass index (BMI), and physical activity. The study focused on self-reported ILD as its outcome measure. The genetic information for ILD was sourced from the FinnGen and UK Biobank (UKB) cohorts. Results The study encompassed a wide range of sample sizes, varying from 64,949 to 632,802, for each risk factor collected from multiple consortia. In total, 593 SNPs were included for all risk factors. The findings revealed significant associations between genetically estimated GERD, dietary factors, BMI, and the risk of ILD within the FinnGen consortium. The odds ratios (ORs) indicated an increase in the risk of ILD per unit of GERD (OR = 1.17, p = 0.001), smoking initiation (OR = 1.10, p < 0.05), BMI (OR = 1.15, p = 0.006), and low-density lipoprotein (LDL) (OR = 1.10, p = 0.02). On the other hand, there was a decrease in the risk of ILD per unit increase in coffee intake (OR = 0.64, p = 0.01) and physical activity (OR = 0.79, p=0.03). Additionally, the results demonstrated a significant association between genetically estimated GERD (OR = 1.01, p < 0.05), coffee intake (OR = 1.14, p=0.03), and high-density lipoproteins (HDL) (OR = 1.01, p=0.04) and increased risk of ILD specifically within the UKB. Conclusions This research indicates that the development of ILDs may be causally associated with GERD and various factors such as coffee intake, smoking, BMI, physical activity, LDL, and HDL These results hold great importance in terms of devising effective strategies for the treatment and prevention of ILDs.