Subsequent Event Risk in Individuals With Established Coronary Heart Disease
Authors: Patel Riyaz S. , Tragante Vinicius , Schmidt Amand F. , McCubrey Raymond O. , Holmes Michael V. , Howe Laurence J. , Direk Kenan , Åkerblom Axel , Leander Karin , Virani Salim S. , Kaminski Karol A. , Muehlschlegel Jochen D. , Allayee Hooman , Almgren Peter , Alver Maris , Baranova Ekaterina V. , Behloui Hassan , Boeckx Bram , Braund Peter S. , Breitling Lutz P. , Delgado Graciela , Duarte Nubia E. , Dubé Marie-Pierre , Dufresne Line , Eriksson Niclas , Foco Luisa , Scholz Markus , Gijsberts Crystel M. , Glinge Charlotte , Gong Yan , Hartiala Jaana , Heydarpour Mahyar , Hubacek Jaroslav A. , Kleber Marcus , Kofink Daniel , Kotti Salma , Kuukasjärvi Pekka , Lee Vei-Vei , Leiherer Andreas , Lenzini Petra A. , Levin Daniel , Lyytikäinen Leo-Pekka , Martinelli Nicola , Mons Ute , Nelson Christopher P. , Nikus Kjell , Pilbrow Anna P. , Ploski Rafal , Sun Yan V. , Tanck Michael W.T. , Tang W.H.Wilson , Trompet Stella , van der Laan Sander W. , Van Setten Jessica , Vilmundarson Ragnar O. , Viviani Anselmi Chiara , Vlachopoulou Efthymia , Al Ali Lawien , Boerwinkle Eric , Briguori Carlo , Carlquist John F. , Carruthers Kathryn F. , Casu Gavino , Deanfield John , Deloukas Panos , Dudbridge Frank , Engstrøm Thomas , Fitzpatrick Natalie , Fox Kim , Gigante Bruna , James Stefan , Lokki Marja-Liisa , Lotufo Paulo A. , Marziliano Nicola , Mordi Ify R. , Muhlestein Joseph B. , Newton-Cheh Christopher , Pitha Jan , Saely Christoph H. , Samman-Tahhan Ayman , Sandesara Pratik B. , Teren Andrej , Timmis Adam , Van de Werf Frans , Wauters Els , Wilde Arthur A.M. , Ford Ian , Stott David J. , Algra Ale , Andreassi Maria G. , Ardissino Diego , Arsenault Benoit J. , Ballantyne Christie M. , Bergmeijer Thomas O. , Bezzina Connie R. , Body Simon C. , Boersma Eric H. , Bogaty Peter , Bots Michiel L. , Brenner Hermann , Brugts Jasper J. , Burkhardt Ralph , Carpeggiani Clara , Condorelli Gianluigi , Cooper-DeHoff Rhonda M. , Cresci Sharon , Danchin Nicolas , de Faire Ulf , Doughty Robert N. , Drexel Heinz , Engert James C. , Fox Keith A.A. , Girelli Domenico , Grobbee Diederick E. , Hagström Emil , Hazen Stanley L. , Held Claes , Hemingway Harry , Hoefer Imo E. , Hovingh G. Kees , Jabbari Reza , Johnson Julie A. , Jukema J. Wouter , Kaczor Marcin P. , Kähönen Mika , Kettner Jiri , Kiliszek Marek , Klungel Olaf H. , Lagerqvist Bo , Lambrechts Diether , Laurikka Jari O. , Lehtimäki Terho , Lindholm Daniel , Mahmoodi B. K. , Maitland-van der Zee Anke H. , McPherson Ruth , Melander Olle , Metspalu Andres , Niemcunowicz-Janica Anna , Olivieri Oliviero , Opolski Grzegorz , Palmer Colin N. , Pasterkamp Gerard , Pepine Carl J. , Pereira Alexandre C. , Pilote Louise , Quyyumi Arshed A. , Richards A. Mark , Sanak Marek , Siegbahn Agneta , Simon Tabassome , Sinisalo Juha , Smith J. Gustav , Spertus John A. , Stender Steen , Stewart Alexandre F.R. , Szczeklik Wojciech , Szpakowicz Anna , Tardif Jean-Claude , ten Berg Jurriën M. , Tfelt-Hansen Jacob , Thanassoulis George , Thiery Joachim , Torp-Pedersen Christian , van der Graaf Yolanda , Visseren Frank L.J. , Waltenberger Johannes , Weeke Peter E. , Van der Harst Pim , Lang Chim C. , Sattar Naveed , Cameron Vicky A. , Anderson Jeffrey L. , Brophy James M. , Pare Guillaume , Horne Benjamin D. , März Winfried , Wallentin Lars , Samani Nilesh J. , Hingorani Aroon D. , Asselbergs Folkert W. 
Published: April 2019

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.