Mendelian randomization study to investigate the causal relationship between plasma homocysteine and chronic obstructive pulmonary disease

Abstract

Abstract Background Several studies have shown an association between plasma homocysteine levels and chronic obstructive pulmonary disease (COPD). It is not clear whether there is a causal association. A two-sample Mendelian randomization (MR) based method was used to further explore the causal association between plasma homocysteine and COPD. Methods Several studies have shown an association between plasma homocysteine levels and COPD. It is not clear whether there is a causal association.we performed a second data analysis using pooled data from published genome-wide association studies (GWASs) .we used genome-wide meta-analysis (n = 44147) to obtain genome-wide single nucleotide polypeptides (SNPs) associated with plasma homocysteine levels as instrumental variables. We used two-sample MR to study plasma homocysteine and COPD and COPD related diseases. MR analysis was performed by the random effects inverse variance weighting method and heterogeneity tests and pleiotropy tests were performed to evaluate the robustness of our findings. Results By two-sample MR analysis, We did not find causal associations between genetically predicted plasma homocysteine levels and COPD and COPD related diseases. In COPD hospital admissions,(OR = 1.06,95%CI 0.91–1.24,P = 0.42),asthma/COPD,(OR = 0.97,95%CI 0.89–1.06, P = 0.55),COPD related to chronic (opportunist) infection(OR = 1.50,95%CI 0.57–3.99,P = 0.41),COPD/asthma/ILD-related pneumonia or pneumonia-derived (OR = 0.93,95%CI 0.86–1.02,P = 0.13),COPD-related respiratory insufficiency(OR = 1.00,95%CI 0.7–1.44,P = 0.99), no heterogeneity and horizontal pleiotropy werefound. Conclusions Our study shows that genetically predicted plasma homocysteine levels are not causally associated with COPD, contrary to previous observational findings.As homocysteine is known to have deleterious effects on endothelial function and vascular homeostasis, further studies are needed to investigate whether additional factors mediate the association between homocysteine and COPD.