Related Experiment Video
Updated: Jun 24, 2025
Identification and Quantification of Deranged Metabolites in Critically Ill Patients Using NMR-Based Metabolomics
Published on: November 29, 2024
Causal relationship between serum metabolites and interstitial lung disease in humans: A mendelian randomization
Tingting Zhao1,1, Tian Lv2,1
1Department of Respiratory and Critical Care Medicine, Zhuji People's Hospital of Zhejiang Province, Zhuji Affiliated Hospital of Wenzhou Medical University, Zhuji, Zhejiang, China.
Background:
A significant proportion of interstitial lung disease (ILD) patients experience two or more comorbidities, leading to an increasing burden of disease, frequent hospitalizations, and premature death.
Objective:
To investigate the causal relationship between serum metabolites and ILD in humans using Mendelian randomization.
Methods:
Genetic loci closely related to human serum metabolites were selected as instrumental variables (IVs), with the inverse-variance weighted method (IVW) as the primary method and the weighted median method (WME) and MR-Egger regression as auxiliary methods for Mendelian randomization analysis of the data. Meanwhile, the causal relationship between human serum metabolites and ILD was evaluated by OR, along with the assessment of the stability and reliability of the results via 3 methods, i.e., heterogeneity testing, gene pleiotropy testing, and sensitivity analysis.
Results:
8,234 single nucleotide polymorphism (SNP) loci were included as IV, among which 23 SNP loci were selected as IV. Specifically, IVW estimated that the risk of ILD in the anti-Jo-1 antibody-positive population was 4.122 times higher than that in the negative population (95% CI: 2.311-5.954, P< 0.001). IVW also supported a causal effect between anti-SSA antibody positivity and ILD (OR = 2.781, 95% CI: 1.413-4.350, P< 0.001). At the same time, MR-Egger fitted a linear relationship between erythrocyte sedimentation rate (ESR) (95% CI: 1.257-5.894, P= 0.002), C-reactive protein (CRP) (95% CI: 2.433-6.935, P= 0.001), and ILD. Additionally, heterogeneity testing with IVW and MR-Egger regression indicated no heterogeneity, and MR-Egger regression intercept and MR-PRESSO testing suggested minimal influence of gene pleiotropy on the results, without non-specific SNPs identified in the leave-one-out analysis.
Conclusion:
A positive causal relationship may exist between anti-Jo-1 antibody positivity, anti-SSA antibody positivity, elevated ESR, elevated CRP, and ILD.
