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

• Published in: Circulation: Genomic and Precision Medicine
• Main Authors: Patel, R, Tragante, V, Schmidt, AF, McCubrey, RO, Holmes, MV, Howe, LJ, Direk, K, Åkerblom, A, Leander, K, Virani, SS, Kaminski, KA, Doughty, RN, Drexel, H, Muehlschlegel, JD, Engert, JC, Fox, KAA, Girelli, D, Grobbee, DE, Hagström, E, Hazen, SL, Held, C, Breitling, LP, Hemingway, H, Hoefer, IE, Hovingh, GK, Allayee, H, Jabbari, R, Johnson, JA, Jukema, JW, Kaczor, MP, Kähönen, M, Kettner, J, Delgado, G, Kiliszek, M, Klungel, OH, Lagerqvist, B, Lambrechts, D, Almgren, P, Laurikka, JO, Lehtimäki, T, Lindholm, D, Mahmoodi, BK, Maitland-van der Zee, AH, Duarte, NE, McPherson, R, Melander, O, Metspalu, A, Niemcunowicz-Janica, A, Olivieri, O, Alver, M, Opolski, G, Palmer, CN, Pasterkamp, G, Pepine, CJ, Dubé, M-P, Pereira, AC, Pilote, L, Quyyumi, AA, Richards, AM, Sanak, M, Siegbahn, A, Baranova, EV, Simon, T, Sinisalo, J, Smith, JG, Dufresne, L, Spertus, JA, Stender, S, Stewart, AFR, Szczeklik, W, Szpakowicz, A, Tardif, J-C, Ten Berg, JM, Behlouli, H, Tfelt-Hansen, J, Thanassoulis, G, Eriksson, N, Thiery, J, Torp-Pedersen, C, van der Graaf, Y, Visseren, FLJ, Waltenberger, J, Weeke, PE, Van der Harst, P, Lang, CC, Boeckx, B, Sattar, N, Foco, L, Cameron, VA, Anderson, JL, Brophy, JM, Paré, G, Horne, BD, März, W, Wallentin, L, Samani, NJ, Hingorani, AD, Braund, PS, Scholz, M, Asselbergs, FW, Gijsberts, CM, Glinge, C, Brugts, JJ, Gong, Y, Hartiala, J, Heydarpour, M, Hubacek, JA, Kleber, M, Kofink, D, Kotti, S, Kuukasjärvi, P, Lee, V-V, Leiherer, A, Burkhardt, R, Lenzini, PA, Levin, D, Lyytikäinen, L-P, Martinelli, N, Mons, U, Nelson, CP, Nikus, K, Pilbrow, AP, Ploski, R, Sun, YV, Carpeggiani, C, 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, Condorelli, G, Briguori, C, Carlquist, JF, Carruthers, KF, Casu, G, Deanfield, J, Deloukas, P, Dudbridge, F, Engström, T, Fitzpatrick, N, Fox, K, Cooper-DeHoff, RM, Gigante, B, James, S, Lokki, M-L, Lotufo, PA, Marziliano, N, Mordi, IR, Muhlestein, JB, Newton-Cheh, C, Pitha, J, Saely, CH, Cresci, S, Samman-Tahhan, A, Sandesara, PB, Teren, A, Timmis, A, Van de Werf, F, Wauters, E, Wilde, AAM, Ford, I, Stott, DJ, Algra, A, Danchin, N, Andreassi, MG, Ardissino, D, Arsenault, BJ, Ballantyne, CM, Bergmeijer, TO, Bezzina, CR, Body, SC, Boersma, EH, Bogaty, P, Bots, M, de Faire, U, Brenner, H
• Format: Article in Journal/Newspaper
• Language: English
• Published: American Heart Association, Lippincott, Williams & Wilkins 2019
• Subjects: myocardial infarction; prognosis; secondary prevention; coronary artery disease; genetics; Nunavut; Yukon; Canada; New Zealand; British Columbia; Myers; Charity; Abbott; Stanton; Collard
• Online Access: https://www.ahajournals.org/doi/10.1161/CIRCGEN.119.002470; http://hdl.handle.net/2381/44553; https://doi.org/10.1161/CIRCGEN.119.002470

The Data Supplement is available at https://www.ahajournals.org/doi/suppl/10.1161/CIRCGEN.119.002470. 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) & Post Myocardial Infarction study (PMI) were funded by the Health Research Council and Heart Foundation of New Zealand; Dr Samman-Tahnan is supported by the National Institutes of Health/National Institutes of Aging grant AG051633; Dr Sandesara is supported by the Abraham J. & Phyllis Katz Foundation (Atlanta, GA); The Emory Cardiovascular Biobank is supported by National Institutes of Health (NIH) grants 5P01HL101398-02, 1P20HL113451-01, 1R56HL126558-01, 1RF1AG051633-01, R01 NS064162-01, R01 HL89650-01, HL095479-01, 1U10HL110302-01, 1DP3DK094346-01, and 2P01HL086773-06A1; The Estonian Biobank was funded by EU H2020 grant 692145, Estonian Research Council Grant IUT20-60, IUT24-6, PUT1660, PUT735, and European Union through the European Regional Development Fund Project No. 2014-2020.4.01.15-0012 GENTRANSMED, NIH-GIANT, ERA-CVD grant Detectin-HF and 2R01DK075787-06A1; FAST-MI (French Registry of Acute ST-Elevation or non–ST-elevation Myocardial Infarction) 2005 is a registry of the French Society of Cardiology, supported by unrestricted grants from Pfizer and Servier. Additional support was obtained from a research grant from the French Caisse Nationale d’Assurance Maladie; GENESIS-PRAXY is funded by the Canadian Institutes of Health Research and Heart and Stroke Foundations of Alberta, NWT & Nunavut, British Columbia and Yukon, Nova Scotia, Ontario, and Quebec (HSFC); The GENDEMIP study was supported by Project (MH, Czech Republic) No. 00023001 (ICEM, Prague); GoDARTS was funded by the Wellcome Trust (072960/Z/03/Z, 084726/Z/08/Z, 084727/Z/08/Z, 085475/Z/08/Z, and 085475/B/08/Z) and as part of the EU IMI-SUMMIT programme. Dr Palmer has received grant funding from the Wellcome Trust to develop the GoDARTS cohort; Dr Mordi is supported by an NHS Education of Scotland/Chief Scientist Office Postdoctoral Clinical Lectureship (PCL 17/07); the GENECOR study was supported in part by the Italian Ministry of Research’s Fund for Basic Research (FIRB 2005); GRACE UK was supported in part by an Educational Grant from Sanofi Aventis; Award from Chief Scientist Office, Scotland; INVEST-GENES was supported by the National Institute of Health Pharmacogenomics Research Network grant U01-GM074492, NIH R01 HL074730, University of Florida Opportunity Fund, BASF Pharma and Abbott Laboratories; IATVB was supported by Epidemiologia e Genetica della Morte Improvvisa in Sardegna; The KAROLA study has received financial support by the German Ministry of Education and Research (01GD9820/0 and 01ER0814), by the Willy-Robert-Pitzer Foundation, and by the Waldburg-Zeil Clinics Isny; The KRAKOW GENIUS Study was supported by a grant from the Polish Ministry of Science and Higher Education, no. NN402083939 and the National Science Centre, no. 2013/09/B/NZ5/00770; LIFE-Heart was funded by the Leipzig Research Center for Civilization Diseases (LIFE). LIFE is an organizational unit affiliated to the Medical Faculty of the University of Leipzig. LIFE is funded by means of the European Union, by the European Regional Development Fund (ERDF) and by funds of the Free State of Saxony within the framework of the excellence initiative; The LURIC study was supported by the 7th Framework Program (AtheroRemo, grant agreement number 201668 and RiskyCAD, grant agreement number 305739) of the European Union; Dr Smith was supported by grants from the European Research Council, Swedish Heart-Lung Foundation, the Swedish Research Council, the Crafoord Foundation, governmental funding of clinical research within the Swedish National Health Service, Skåne University Hospital in Lund, and the Scania county, a generous donation from the Knut and Alice Wallenberg foundation to the Wallenberg Center for Molecular Medicine at Lund University, and funding from the Swedish Research Council and Swedish Foundation for Strategic Research to the Lund University Diabetes Center; The NEAPOLIS CAMPANIA study was suppported by European Research Council Advanced Grant (CardioEpigen, no. 294609); Italian Ministry of Health (PE-2013-02356818); Italian Ministry of Education, University and Research (2015583WMX); The North East Poland Myocardial Infarction Study was supported by grant no. 402 529139 from the National Science Center (Poland); Dr Vilmundarson is supported by a graduate fellowship of the University of Ottawa Heart Institute; OHGS was funded in part by a Heart and Stroke Foundation grant; Dr Stott was supported in part by an investgator initiated grant from Bristol Myers Squibb; The PROSPER study was supported by an investigator initiated grant obtained from Bristol-Myers Squibb. Dr Jukema is an Established Clinical Investigator of the Netherlands Heart Foundation (grant 2001 D 032). Support for genotyping was provided by the seventh framework program of the European commission (grant 223004) and by the Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging grant 050-060-810).; The RISCA study was supported in part by FRSQ, HSFC, Merck Frost Canada, Pfizer Canada; The SHEEP study was supported by grants from the Swedish Council for Work Life and Social Research, and the Stockholm County Council; The TNT trial was sponsored by Pfizer who granted access to data, Genotyping of the samples was funded in part by grants from Genome Canada and Genome Quebec and the Canadian Institutes of Health Research (CIHR); Dr Arsenault holds a junior scholar award from the Fonds de recherche du Quebec-Sante (FRQS); Dr Cresci is supported, in part, by the National Institutes of Health (Cresci R01 NR013396). The TRIUMPH study was sponsored by the National Institutes of Health: Washington University School of Medicine SCCOR Grant P50 HL077113; The UCP studies were funded by the Netherlands Heart Foundation and the Dutch Top Institute Pharma Mondriaan Project; The Verona Heart Study was supported by the Cariverona Foundation; Veneto Region; Italian Ministry of Education, University, and Research (MIUR); LURM (Laboratorio Universitario di Ricerca Medica) Research Center, University of Verona; The Warsaw ACS Registry is supported by grant No. R13 0001 06 from The National Centre for Research and Development (NCBiR), Statutory Grant from Medical University of Warsaw; Dr Nelson is funded by the British Heart Foundation; Dr Samani is funded by the British Heart Foundation and is a NIHR Senior Investigator; Dr Hingorani is a NIHR Senior Investigator. Dr Asselbergs is supported by UCL Hospitals NIHR Biomedical Research Centre, EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart grant no. 116074, the European Union’s Horizon 2020 research and innovation programme under the ERA-NET Co-fund action No. 01KL1802 (Druggable-MI-gene) jointly funded by the Dutch Heart Foundation and Netherlands Organization for Health Research and Development (ZonMw). Peer-reviewed Publisher Version