Genetic Insights into Glycine's Protective Role Against CAD - European and East Asia, 2015 and 2020.

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.