Subsequent Event Risk in Individuals with Established Coronary Heart Disease: Design and Rationale of the GENIUS-CHD Consortium

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Riyaz Patel, Vinicius Tragante, Amand F Schmidt, Raymond O McCubrey, Michael V Holmes, Laurence J Howe, Kenan Direk, Axel Åkerblom, Karin Leander, Salim S Virani, Karol A Kaminski, Jochen D Muehlschlegel, Hooman Allayee, Peter Almgren, Maris Alver, Ekaterina V Baranova, Hassan Behlouli, Bram Boeckx, Peter S Braund, Lutz P Breitling & 161 others Graciela Delgado, Nubia E Duarte, Marie-Pierre Dubé, Line Dufresne, Niclas Eriksson, Luisa Foco, Markus Scholz, Crystel M Gijsberts, Charlotte Glinge, Yan Gong, Jaana Hartiala, Mahyar Heydarpour, Jaroslav A Hubacek, Marcus Kleber, Daniel Kofink, Salma Kotti, Pekka Kuukasjärvi, Vei-Vei Lee, Andreas Leiherer, Petra A Lenzini, Daniel Levin, Leo-Pekka Lyytikäinen, Nicola Martinelli, Ute Mons, Christopher P Nelson, Kjell Nikus, Anna P Pilbrow, Rafal Ploski, Yan V Sun, Michael W T Tanck, W H Wilson Tang, Stella Trompet, Sander W van der Laan, Jessica Van Setten, Ragnar O Vilmundarson, Chiara Viviani Anselmi, Efthymia Vlachopoulou, Lawien Al Ali, Eric Boerwinkle, Carlo Briguori, John F Carlquist, Kathryn F Carruthers, Gavino Casu, John Deanfield, Panos Deloukas, Frank Dudbridge, Thomas Engström, Natalie Fitzpatrick, Kim Fox, Bruna Gigante, Stefan James, Marja-Liisa Lokki, Paulo A Lotufo, Nicola Marziliano, Ify R Mordi, Joseph B Muhlestein, Christopher Newton-Cheh, Jan Pitha, Christoph H Saely, Ayman Samman-Tahhan, Pratik B Sandesara, Andrej Teren, Adam Timmis, Frans Van de Werf, Els Wauters, Arthur A M Wilde, Ian Ford, David J Stott, Ale Algra, Maria G Andreassi, Diego Ardissino, Benoit J Arsenault, Christie M Ballantyne, Thomas O Bergmeijer, Connie R Bezzina, Simon C Body, Eric H Boersma, Peter Bogaty, Michiel Bots, Hermann Brenner, Jasper J Brugts, Ralph Burkhardt, Clara Carpeggiani, Gianluigi Condorelli, Rhonda M Cooper-DeHoff, Sharon Cresci, Nicolas Danchin, Ulf de Faire, Robert N Doughty, Heinz Drexel, James C Engert, Keith A A Fox, Domenico Girelli, Diederick E Grobbee, Emil Hagström, Stanley L Hazen, Claes Held, Harry Hemingway, Imo E Hoefer, G Kees Hovingh, Reza Jabbari, Julie A Johnson, J Wouter Jukema, Marcin P Kaczor, Mika Kähönen, Jiri Kettner, Marek Kiliszek, Olaf H Klungel, Bo Lagerqvist, Diether Lambrechts, Jari O Laurikka, Terho Lehtimäki, Daniel Lindholm, B K Mahmoodi, Anke H Maitland-van der Zee, Ruth McPherson, Olle Melander, Andres Metspalu, Anna Niemcunowicz-Janica, Oliviero Olivieri, Grzegorz Opolski, Colin N Palmer, Gerard Pasterkamp, Carl J Pepine, Alexandre C Pereira, Louise Pilote, Arshed A Quyyumi, A Mark Richards, Marek Sanak, Agneta Siegbahn, Tabassome Simon, Juha Sinisalo, J Gustav Smith, John A Spertus, Steen Stender, Alexandre F R Stewart, Wojciech Szczeklik, Anna Szpakowicz, Jean-Claude Tardif, Jurriën M Ten Berg, Jacob Tfelt-Hansen, George Thanassoulis, Joachim Thiery, Christian Torp-Pedersen, Yolanda van der Graaf, Frank L J Visseren, Johannes Waltenberger, Peter E Weeke, Pim Van der Harst, Chim C Lang, Naveed Sattar, Vicky A Cameron, Jeffrey L Anderson, James M Brophy, Guillaume Paré, Benjamin D Horne, Winfried März, Lars Wallentin, Nilesh J Samani, Aroon D Hingorani, Folkert W Asselbergs

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 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 (HR 1.15 95% CI 1.14-1.16) per 5-year increase, male sex (HR 1.17, 95% CI 1.13-1.21) and smoking (HR 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 non-genetic determinants of subsequent event risk in individuals with established CHD, in order 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.

Original languageEnglish
JournalCirculation. Genomic and precision medicine
ISSN2574-8300
DOIs
Publication statusE-pub ahead of print - 21 Mar 2019

ID: 216911904