Abstract
The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events. Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints. GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
Highlights
The Genetics of Subsequent Coronary Heart Disease (GENIUS-coronary heart disease (CHD)) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD
Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age per 5-year increase, male sex and smoking with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints
Brief narrative descriptions of each study are provided in Methods in the Data Supplement
Summary
The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. In accordance with Transparency and Openness Promotion Guidelines, the data, analytic methods, and study materials will be made available to other researchers for purposes of reproducing the results or replicating the procedures. Participating studies received local institutional review board approval and included patients who had provided informed consent at the time of enrollment. The central analysis sites received waivers from their local institutional review board for collating and analyzing summary-level data from these individual studies. Full details on the eligibility criteria, definitions of terminology, management of the consortium, and planned projects are provided in Materials in the Data Supplement
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