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

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posted on 2019-06-21, 15:04 authored by R Patel, V Tragante, AF Schmidt, RO McCubrey, MV Holmes, LJ Howe, K Direk, A Åkerblom, K Leander, SS Virani, KA Kaminski, RN Doughty, H Drexel, JD Muehlschlegel, JC Engert, KAA Fox, D Girelli, DE Grobbee, E Hagström, SL Hazen, C Held, LP Breitling, H Hemingway, IE Hoefer, GK Hovingh, H Allayee, R Jabbari, JA Johnson, JW Jukema, MP Kaczor, M Kähönen, J Kettner, G Delgado, M Kiliszek, OH Klungel, B Lagerqvist, D Lambrechts, P Almgren, JO Laurikka, T Lehtimäki, D Lindholm, BK Mahmoodi, AH Maitland-van der Zee, NE Duarte, R McPherson, O Melander, A Metspalu, A Niemcunowicz-Janica, O Olivieri, M Alver, G Opolski, CN Palmer, G Pasterkamp, CJ Pepine, M-P Dubé, AC Pereira, L Pilote, AA Quyyumi, AM Richards, M Sanak, A Siegbahn, EV Baranova, T Simon, J Sinisalo, JG Smith, L Dufresne, JA Spertus, S Stender, AFR Stewart, W Szczeklik, A Szpakowicz, J-C Tardif, JM Ten Berg, H Behlouli, J Tfelt-Hansen, G Thanassoulis, N Eriksson, J Thiery, C Torp-Pedersen, Y van der Graaf, FLJ Visseren, J Waltenberger, PE Weeke, P Van der Harst, CC Lang, B Boeckx, N Sattar, L Foco, VA Cameron, JL Anderson, JM Brophy, G Paré, BD Horne, W März, L Wallentin, NJ Samani, AD Hingorani, PS Braund, M Scholz, FW Asselbergs, CM Gijsberts, C Glinge, JJ Brugts, Y Gong, J Hartiala, M Heydarpour, JA Hubacek, M Kleber, D Kofink, S Kotti, P Kuukasjärvi, V-V Lee, A Leiherer, R Burkhardt, PA Lenzini, D Levin, L-P Lyytikäinen, N Martinelli, U Mons, CP Nelson, K Nikus, AP Pilbrow, R Ploski, YV Sun, C Carpeggiani, MWT Tanck, WHW Tang, S Trompet, SW van der Laan, J Van Setten, RO Vilmundarson, C Viviani Anselmi, E Vlachopoulou, L Al Ali, E Boerwinkle, G Condorelli, C Briguori, JF Carlquist, KF Carruthers, G Casu, J Deanfield, P Deloukas, F Dudbridge, T Engström, N Fitzpatrick, K Fox, RM Cooper-DeHoff, B Gigante, S James, M-L Lokki, PA Lotufo, N Marziliano, IR Mordi, JB Muhlestein, C Newton-Cheh, J Pitha, CH Saely, S Cresci, A Samman-Tahhan, PB Sandesara, A Teren, A Timmis, F Van de Werf, E Wauters, AAM Wilde, I Ford, DJ Stott, A Algra, N Danchin, MG Andreassi, D Ardissino, BJ Arsenault, CM Ballantyne, TO Bergmeijer, CR Bezzina, SC Body, EH Boersma, P Bogaty, M Bots, U de Faire, H Brenner
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.


The funder(s) of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Within GENIUS-CHD, all participating investigators and sponsors who contributed data and analyses are acknowledged irrespective of academic or industry affiliations. Specific funding statements: Dr Patel is funded by a British Heart Foundation Intermediate Fellowship (FS/14/76/30933). This research was also supported by the National Institute for Health Research University College London Hospitals Biomedical Research Center; Dr Schmidt is funded by BHF grant PG/18/5033837; Dr Holmes works in a unit that receives funding from the UK Medical Research Council and is supported by a British Heart Foundation Intermediate Clinical Research Fellowship (FS/18/23/33512) and the National Institute for Health Research Oxford Biomedical Research Center; The AGNES study (Arrhythmia Genetics in The Netherlands) was supported by research grants from the Netherlands Heart Foundation (2001D019, 2003T302, 2007B202, and the PREDICT project [CVON 2012-10]), the Leducq Foundation (grant 05-CVD) and the Center for Translational Molecular Medicine (CTMM COHFAR).; The Cleveland Clinic Genebank Study was supported in part by NIH grants R0133169, R01ES021801, R01MD010358, and R01ES025786, R01HL103866, R01DK106000, R01HL126827, P20HL113452, P01HL098055, P01HL076491, and R01HL103931; The Clinical Cohorts in Coronary disease Collaboration (4C) study was supported in part by National Institute for Health Research (NIHR) and Barts Charity; The Corogene study was supported by grants from Aarno Koskelo Foundation, Helsinki University Central Hospital special government funds (EVO nos. TYH7215, TKK2012005, TYH2012209, and TYH2014312), and Finnish Foundation for Cardiovascular research; CABGenomics was supported by Stanton Shernan, C. David Collard, Amanda A. Fox/R01 HL 098601 National Heart, Lung, and Blood Institute (NHLBI); The Coronary Disease Cohort Study (CDCS) &



Circulation: Genomic and Precision Medicine, 2019;12:e002470.

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Circulation: Genomic and Precision Medicine


American Heart Association, Lippincott, Williams & Wilkins



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