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Patel RS, Tragante V, Schmidt AF, McCubrey RO, Holmes MV, Howe LJ, Direk K, Åkerblom A, Leander K, Virani SS, Kaminski KA, Muehlschlegel JD, Allayee H, Almgren P, Alver M, Baranova EV, Behloui H, Boeckx B, Braund PS, Breitling LP, Delgado G, Duarte NE, Dubé MP, Dufresne L, Eriksson N, Foco L, Scholz M, Gijsberts CM, Glinge C, Gong Y, Hartiala J, Heydarpour M, Hubacek JA, Kleber M, Kofink D, Kotti S, Kuukasjärvi P, Lee VV, Leiherer A, Lenzini PA, Levin D, Lyytikäinen LP, Martinelli N, Mons U, Nelson CP, Nikus K, Pilbrow AP, Ploski R, Sun YV, Tanck MWT, Tang WHW, Trompet S, van der Laan SW, Van Setten J, Vilmundarson RO, Viviani Anselmi C, Vlachopoulou E, Al Ali L, Boerwinkle E, Briguori C, Carlquist JF, Carruthers KF, Casu G, Deanfield J, Deloukas P, Dudbridge F, Engstrøm T, Fitzpatrick N, Fox K, Gigante B, James S, Lokki ML, Lotufo PA, Marziliano N, Mordi IR, Muhlestein JB, Newton-Cheh C, Pitha J, Saely CH, Samman-Tahhan A, Sandesara PB, Teren A, Timmis A, Van de Werf F, Wauters E, Wilde AAM, Ford I, Stott DJ, Algra A, Andreassi MG, Ardissino D, Arsenault BJ, Ballantyne CM, Bergmeijer TO, Bezzina CR, Body SC, Boersma EH, Bogaty P, Bots ML, Brenner H, Brugts JJ, Burkhardt R, Carpeggiani C, Condorelli G, Cooper-DeHoff RM, Cresci S, Danchin N, de Faire U, Doughty RN, Drexel H, Engert JC, Fox KAA, Girelli D, Grobbee DE, Hagström E, Hazen SL, Held C, Hemingway H, Hoefer IE, Hovingh GK, Jabbari R, Johnson JA, Jukema JW, Kaczor MP, Kähönen M, Kettner J, Kiliszek M, Klungel OH, Lagerqvist B, Lambrechts D, Laurikka JO, Lehtimäki T, Lindholm D, Mahmoodi BK, Maitland-van der Zee AH, McPherson R, Melander O, Metspalu A, Niemcunowicz-Janica A, Olivieri O, Opolski G, Palmer CN, Pasterkamp G, Pepine CJ, Pereira AC, Pilote L, Quyyumi AA, Richards AM, Sanak M, Siegbahn A, Simon T, Sinisalo J, Smith JG, Spertus JA, Stender S, Stewart AFR, Szczeklik W, Szpakowicz A, Tardif JC, Ten Berg JM, Tfelt-Hansen J, Thanassoulis G, Thiery J, Torp-Pedersen C, van der Graaf Y, Visseren FLJ, Waltenberger J, Weeke PE, Van der Harst P, Lang CC, Sattar N, Cameron VA, Anderson JL, Brophy JM, Pare G, Horne BD, März W, Wallentin L, Samani NJ, Hingorani AD, Asselbergs FW. Subsequent Event Risk in Individuals With Established Coronary Heart Disease. Circulation. Genomic and precision medicine. 2019 Apr 1; 12(4):e002470.
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Abstract: BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.