Introduction:The purpose of this study is to examine the potential causal relationship between levels of circulating glycine and coronary artery disease(CAD)using a two-step Mendelian randomization(MR)analysis.Methods...Introduction:The purpose of this study is to examine the potential causal relationship between levels of circulating glycine and coronary artery disease(CAD)using a two-step Mendelian randomization(MR)analysis.Methods:We analyzed data from genome-wide association studies(GWAS)conducted on European and East Asian populations.To assess the causal effects of circulating glycine levels on the risk of CAD.We used the inverse-variance weighting(IVW),weighted median(WM),MR-Egger,and Mendelian Randomization Pleiotropy RESidual Sum and Outlier(MR-PRESSO)methods.Furthermore,we conducted mediation analysis to investigate the contribution of blood pressure and other cardiovascular disease-related traits.Results:The two-step Mendelian randomization analysis revealed that higher levels of glycine in the blood were associated with a reduced risk of CAD in Europeans[odds ratio(OR)=0.84,95%confidence interval(CI):0.72,−0.98;P=0.029]and East Asians:(OR=0.76,95%CI:0.66,−0.89;P=3.57×10−4).Sensitivity analysis confirmed the robustness of these findings.Additionally,our results suggest that about 6.06%of the observed causal effect is mediated through genetically predicted systolic blood pressure(SBP)in the European population.Discussion:Our results contribute to the current knowledge regarding the involvement of glycine in the progression of CAD,and provide valuable methodological insights for the prevention and treatment of this condition.展开更多
基金Supported by the National Natural Science Foundation of China(82273612),and by Open Project of Key Laboratory of Science and Engineering for the Multi-Modal Prevention and Control of Major Chronic Diseases,Ministry of Industry and Information Technology(Grant No.MCD-2023-1-09).
文摘Introduction:The purpose of this study is to examine the potential causal relationship between levels of circulating glycine and coronary artery disease(CAD)using a two-step Mendelian randomization(MR)analysis.Methods:We analyzed data from genome-wide association studies(GWAS)conducted on European and East Asian populations.To assess the causal effects of circulating glycine levels on the risk of CAD.We used the inverse-variance weighting(IVW),weighted median(WM),MR-Egger,and Mendelian Randomization Pleiotropy RESidual Sum and Outlier(MR-PRESSO)methods.Furthermore,we conducted mediation analysis to investigate the contribution of blood pressure and other cardiovascular disease-related traits.Results:The two-step Mendelian randomization analysis revealed that higher levels of glycine in the blood were associated with a reduced risk of CAD in Europeans[odds ratio(OR)=0.84,95%confidence interval(CI):0.72,−0.98;P=0.029]and East Asians:(OR=0.76,95%CI:0.66,−0.89;P=3.57×10−4).Sensitivity analysis confirmed the robustness of these findings.Additionally,our results suggest that about 6.06%of the observed causal effect is mediated through genetically predicted systolic blood pressure(SBP)in the European population.Discussion:Our results contribute to the current knowledge regarding the involvement of glycine in the progression of CAD,and provide valuable methodological insights for the prevention and treatment of this condition.
