Subsequent Event Risk in Individuals With Established Coronary Heart Disease: Design and Rationale of the GENIUS-CHD Consortium.
Patel, Riyaz S. MD ,,*; Tragante, Vinicius PhD ,*; Schmidt, Amand F. PhD ,,*; McCubrey, Raymond O. MS; Holmes, Michael V. MD, PhD; Howe, Laurence J. PhD; Direk, Kenan PhD; Akerblom, Axel MD, PhD; Leander, Karin PhD; Virani, Salim S. MD, PhD; Kaminski, Karol A. MD, PhD; Muehlschlegel, Jochen D. MD, MMSc; Allayee, Hooman PhD; Almgren, Peter MSc; Alver, Maris MSc; Baranova, Ekaterina V. MSc; Behloui, Hassan PhD; Boeckx, Bram PhD; Braund, Peter S. PhD; Breitling, Lutz P. MD; Delgado, Graciela MSc; Duarte, Nubia E. PhD; Dube, Marie-Pierre PhD; Dufresne, Line MSc; Eriksson, Niclas PhD; Foco, Luisa PhD; Scholz, Markus PhD; Gijsberts, Crystel M. MD, PhD; Glinge, Charlotte MD; Gong, Yan PhD; Hartiala, Jaana PhD; Heydarpour, Mahyar PhD; Hubacek, Jaroslav A. DSc; Kleber, Marcus PhD; Kofink, Daniel PhD; Kotti, Salma PharmD, PhD; Kuukasjarvi, Pekka PhD; Lee, Vei-Vei MS; Leiherer, Andreas PhD; Lenzini, Petra A. MS; Levin, Daniel PhD; Lyytikainen, Leo-Pekka MD; Martinelli, Nicola MD, PhD; Mons, Ute PhD; Nelson, Christopher P. PhD; Nikus, Kjell PhD; Pilbrow, Anna P. PhD; Ploski, Rafal MD, PhD; Sun, Yan V. PhD; Tanck, Michael W.T. PhD; Tang, W.H.Wilson MD; Trompet, Stella PhD; van der Laan, Sander W. PhD; Van Setten, Jessica PhD; Vilmundarson, Ragnar O. MSc; Viviani Anselmi, Chiara PhD; Vlachopoulou, Efthymia PhD; Al Ali, Lawien MD; Boerwinkle, Eric PhD; Briguori, Carlo MD, PhD; Carlquist, John F. PhD; Carruthers, Kathryn F. MPhil; Casu, Gavino MD; Deanfield, John MD; Deloukas, Panos PhD; Dudbridge, Frank PhD; Engstrom, Thomas MD, PhD; Fitzpatrick, Natalie MSc; Fox, Kim MD, PhD; Gigante, Bruna PhD; James, Stefan MD, PhD; Lokki, Marja-Liisa PhD; Lotufo, Paulo A. MD, PhD; Marziliano, Nicola PhD; Mordi, Ify R. MD; Muhlestein, Joseph B. MD; Newton-Cheh, Christopher MD; Pitha, Jan PhD; Saely, Christoph H. MD; Samman-Tahhan, Ayman MD; Sandesara, Pratik B. MD; Teren, Andrej MD; Timmis, Adam MD; Van de Werf, Frans PhD; Wauters, Els PhD; Wilde, Arthur A.M. MD, PhD; Ford, Ian MD, PhD; Stott, David J. MD; Algra, Ale MD; Andreassi, Maria G. PhD; Ardissino, Diego MD; Arsenault, Benoit J. PhD; Ballantyne, Christie M. MD; Bergmeijer, Thomas O. MD; Bezzina, Connie R. PhD; Body, Simon C. MBChB, MPH; Boersma, Eric H. MD, PhD; Bogaty, Peter MD; Bots, Michiel L. MD; Brenner, Hermann MD, PhD; Brugts, Jasper J. MD, PhD; Burkhardt, Ralph MD; Carpeggiani, Clara MD; Condorelli, Gianluigi MD, PhD; Cooper-DeHoff, Rhonda M. PharmD; Cresci, Sharon MD; Danchin, Nicolas MD, PhD; de Faire, Ulf PhD; Doughty, Robert N. MD; Drexel, Heinz MD; Engert, James C. PhD; Fox, Keith A.A. MD, PhD; Girelli, Domenico MD, PhD; Grobbee, Diederick E. MD, PhD; Hagstrom, Emil MD, PhD; Hazen, Stanley L. MD, PhD; Held, Claes MD, PhD; Hemingway, Harry MD, PhD; Hoefer, Imo E. MD, PhD; Hovingh, G. Kees MD, PhD; Jabbari, Reza MD, PhD; Johnson, Julie A. PharmD; Jukema, J. Wouter MD, PhD; Kaczor, Marcin P. MD, PhD; Kahonen, Mika PhD; Kettner, Jiri PhD; Kiliszek, Marek MD, PhD; Klungel, Olaf H. PharmD, PhD; Lagerqvist, Bo MD, PhD; Lambrechts, Diether PhD; Laurikka, Jari O. PhD; Lehtimaki, Terho PhD; Lindholm, Daniel MD, PhD; Mahmoodi, B. K. MD, PhD; Maitland-van der Zee, Anke H. PharmD, PhD; McPherson, Ruth MD, PhD; Melander, Olle MD, PhD; Metspalu, Andres MD, PhD; Niemcunowicz-Janica, Anna MD, PhD; Olivieri, Oliviero MD; Opolski, Grzegorz MD, PhD; Palmer, Colin N. PhD; Pasterkamp, Gerard MD, PhD; Pepine, Carl J. MD; Pereira, Alexandre C. MD, PhD; Pilote, Louise MD; Quyyumi, Arshed A. MD; Richards, A. Mark MD, PhD; Sanak, Marek MD, PhD; Siegbahn, Agneta MD, PhD; Simon, Tabassome MD, PhD; Sinisalo, Juha MD, PhD; Smith, J. Gustav MD, PhD; Spertus, John A. MD, MPH; Stender, Steen MD, DSc; Stewart, Alexandre F.R. PhD; Szczeklik, Wojciech MD, PhD; Szpakowicz, Anna MD, PhD; Tardif, Jean-Claude MD; ten Berg, Jurrien M. MD, PhD; Tfelt-Hansen, Jacob MD, DMSc; Thanassoulis, George MD; Thiery, Joachim MD; Torp-Pedersen, Christian MD, DSc; van der Graaf, Yolanda MD; Visseren, Frank L.J. MD; Waltenberger, Johannes MD; Weeke, Peter E. MD, PhD; Van der Harst, Pim MD, PhD; Lang, Chim C. MD; Sattar, Naveed PhD; Cameron, Vicky A. PhD; Anderson, Jeffrey L. MD; Brophy, James M. MD; Pare, Guillaume MD; Horne, Benjamin D. PhD, MPH; Marz, Winfried MD; Wallentin, Lars MD, PhD; Samani, Nilesh J. MD, PhD ,,+; Hingorani, Aroon D. MD, PhD ,+; Asselbergs, Folkert W. MD, PhD ,,,+
Circulation: Genomic and Precision Medicine.
12(4):e002470, April 2019.
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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.
(C) 2019 American Heart Association, Inc.