The study investigates the role of the interleukin-6 receptor (IL6R) in preventing coronary heart disease (CHD) using Mendelian randomization. It combines genetic data from 26 prospective studies, four randomized cardiovascular prevention trials, two cross-sectional studies, and eight retrospective case-control studies. The analysis focuses on the association between IL6R genetic variants and CHD risk, as well as inflammatory biomarkers like CRP, fibrinogen, and IL-6. Key findings include that the IL6R variant rs7529229 is associated with higher circulating IL-6 levels, while rs4845371 and rs12740969 are linked to lower levels. The study also examines the effects of tocilizumab, an IL-6 receptor inhibitor, on CRP levels in treatment trials and non-randomized studies. The results suggest that IL6R variants may influence CHD risk, with rs7529229 showing a protective effect against fatal and non-fatal CHD. The study highlights the importance of IL-6 signaling in cardiovascular disease and provides insights into potential therapeutic targets for prevention. The analysis includes detailed methods for SNP selection, genotyping, and statistical analysis, as well as subgroup analyses by age, sex, and other clinical factors. The study contributes to understanding the genetic basis of CHD and the role of IL-6 in cardiovascular health.The study investigates the role of the interleukin-6 receptor (IL6R) in preventing coronary heart disease (CHD) using Mendelian randomization. It combines genetic data from 26 prospective studies, four randomized cardiovascular prevention trials, two cross-sectional studies, and eight retrospective case-control studies. The analysis focuses on the association between IL6R genetic variants and CHD risk, as well as inflammatory biomarkers like CRP, fibrinogen, and IL-6. Key findings include that the IL6R variant rs7529229 is associated with higher circulating IL-6 levels, while rs4845371 and rs12740969 are linked to lower levels. The study also examines the effects of tocilizumab, an IL-6 receptor inhibitor, on CRP levels in treatment trials and non-randomized studies. The results suggest that IL6R variants may influence CHD risk, with rs7529229 showing a protective effect against fatal and non-fatal CHD. The study highlights the importance of IL-6 signaling in cardiovascular disease and provides insights into potential therapeutic targets for prevention. The analysis includes detailed methods for SNP selection, genotyping, and statistical analysis, as well as subgroup analyses by age, sex, and other clinical factors. The study contributes to understanding the genetic basis of CHD and the role of IL-6 in cardiovascular health.