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Genetic causal association between metabolic syndrome and idiopathic pulmonary fibrosis: A 2-sample Mendelian
1Department of Respiratory Medicine, The Second Affiliated Hospital, University of South China, Hengyang City, Hunan Province, China.
Abstract:
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.
Insights
Metabolic syndrome (MetS) components like waist circumference and high-density lipoprotein cholesterol may causally influence idiopathic pulmonary fibrosis (IPF). Further research is needed to confirm these links for IPF prevention and treatment.
Area of Science:
- Pulmonary Medicine
- Metabolic Health
- Genetics
Background:
- Epidemiological studies suggest a link between metabolic syndrome (MetS) and idiopathic pulmonary fibrosis (IPF).
- The precise inherited causal relationship between MetS and IPF remains unclear.
- Understanding this link is crucial for potential therapeutic targets and prevention strategies for IPF.
Purpose of the Study:
- To investigate the potential inherited causal effect of metabolic syndrome and its components on idiopathic pulmonary fibrosis.
- To differentiate the causal roles of individual MetS components versus MetS as a whole in IPF etiology.
- To utilize robust genetic methods to establish or refute a causal link between metabolic factors and IPF.
Main Methods:
- A two-sample Mendelian randomization (MR) design was employed.
- Multiple analytical strategies including IVW, MR-Egger, weighted median, and weighted mode were used.
- Tests for heterogeneity (Cochran's Q) and pleiotropy (MR-Egger intercept, MR-PRESSO) were conducted to ensure result validity.
Main Results:
- A potential causal association was observed between increased waist circumference and IPF (OR: 1.0016, P=0.001) via IVW analysis, though not consistently across all models.
- High-density lipoprotein cholesterol showed a consistent positive association with IPF across IVW, MR-Egger, and weighted mode analyses (OR: 1.0006, P=0.033).
- No significant genetic causal associations were found for MetS as a whole, essential hypertension, fasting blood glucose, or triglycerides with IPF.
Conclusions:
- Metabolic traits, specifically waist circumference and high-density lipoprotein cholesterol, may have a causal influence on the development of idiopathic pulmonary fibrosis.
- Metabolic syndrome as a composite condition did not show a direct genetic causal link to IPF in this study.
- These findings highlight specific metabolic factors as potential targets for future research in IPF prevention and treatment strategies.
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