Genetic causal association between metabolic syndrome and idiopathic pulmonary fibrosis: A 2-sample Mendelian randomization

Prior epidemiological investigations have indicated a linkage between metabolic syndrome (MetS) and idiopathic pulmonary fibrosis (IPF). The objective of the present research was to elucidate the inherited causal relationship of MetS with IPF. A 2-sample Mendelian randomization (MR) design was adopted to assess the genetic cause-effect link between MetS and IPF. Multiple analytical strategies, such as inverse-variance weighted (IVW), MR-Egger, weighted median, and weighted mode, were implemented. Outlier evaluation was carried out through a leave-one-out analysis. MR-PRESSO and the MR-Egger intercept test were undertaken to reduce the influence of horizontal pleiotropy. Heterogeneity was appraised using Cochran's Q statistic. IVW analysis suggested a potential causal association between waist circumference and IPF (odds ratio: 1.0016, 95% confidence interval: 1.0006-1.0025, P = .001), although this association was not consistently observed in other MR models. By contrast, high-density lipoprotein cholesterol showed a more consistent positive association with IPF, supported by IVW, MR-Egger, and weighted mode analyses (odds ratio: 1.0006, 95% confidence interval: 1.0001-1.0012, P = .033) The heterogeneity test results indicated that our IVW analysis findings exhibited minimal presence of heterogeneity (P > .05). The results of the pleiotropy test showed that there was no pleiotropy in our results (P > .05). No genetic causal association was found for MetS as a whole, essential hypertension, fasting blood glucose, or triglycerides with IPF. This study indicates a potential causal link between metabolic traits such as waist circumference and high-density lipoprotein cholesterol with IPF. Future clinical research is warranted to further confirm these associations and to clarify their relevance in IPF prevention and treatment.