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Subsequent Event Risk in Individuals With Established Coronary Heart Disease: Design and Rationale of the GENIUS-CHD Consortium
UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England;St Bartholomews Hosp, Barts Heart Ctr, London, England.
UMC Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands.
UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England;UMC Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands.
Intermt Med Ctr, Intermt Heart Inst, Salt Lake City, UT USA.
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2019 (English)In: Circulation: Genomic and Precision Medicine, ISSN 2574-8300, Vol. 12, no 4, article id e002470Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2019. Vol. 12, no 4, article id e002470
Keywords [en]
coronary artery disease, genetics, myocardial infarction, prognosis, secondary prevention
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:uu:diva-383875DOI: 10.1161/CIRCGEN.119.002470ISI: 000466741600004PubMedID: 30896328OAI: oai:DiVA.org:uu-383875DiVA, id: diva2:1323765
Funder
EU, FP7, Seventh Framework Programme, 201668EU, FP7, Seventh Framework Programme, 305739EU, European Research Council, 294609Swedish Research CouncilSwedish Foundation for Strategic Research EU, European Research Council, 294609EU, Horizon 2020, 01KL1802NIH (National Institute of Health), R0133169NIH (National Institute of Health), R01ES021801NIH (National Institute of Health), R01MD010358NIH (National Institute of Health), R01ES025786NIH (National Institute of Health), R01HL103866NIH (National Institute of Health), R01DK106000NIH (National Institute of Health), R01HL126827NIH (National Institute of Health), P20HL113452NIH (National Institute of Health), P01HL098055NIH (National Institute of Health), P01HL076491NIH (National Institute of Health), R01HL103931NIH (National Institute of Health), AG051633NIH (National Institute of Health), 5P01HL101398-02NIH (National Institute of Health), 1P20HL113451-01NIH (National Institute of Health), 1R56HL126558-01NIH (National Institute of Health), 1RF-1AG051633-01NIH (National Institute of Health), R01 NS064162-01NIH (National Institute of Health), R01 HL89650-01NIH (National Institute of Health), HL095479-01NIH (National Institute of Health), 1U10HL110302-01NIH (National Institute of Health), 1DP3DK094346-01NIH (National Institute of Health), 2P01HL086773-06A1EU, Horizon 2020, 692145Wellcome trust, 072960/Z/03/ZWellcome trust, 084726/Z/08/ZWellcome trust, 084727/Z/08/ZWellcome trust, 085475/Z/08/ZWellcome trust, 085475/B/08/ZSwedish Heart Lung FoundationThe Crafoord FoundationKnut and Alice Wallenberg FoundationEU, FP7, Seventh Framework Programme, 223004Forte, Swedish Research Council for Health, Working Life and WelfareNIH (National Institute of Health), R01 NR013396Available from: 2019-06-12 Created: 2019-06-12 Last updated: 2019-06-12Bibliographically approved

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Åkerblom, AxelEriksson, NiclasJames, StefanHagström, EmilHeld, ClaesLagerqvist, BoLindholm, DanielSiegbahn, AgnetaWallentin, Lars

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