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.

5th Department of Medicine Medical Faculty Mannheim Heidelberg University Germany

Amsterdam UMC University of Amsterdam Clinical and Experimental Cardiology Amsterdam Cardiovascular Sciences AMC Heart Center the Netherlands

Amsterdam UMC University of Amsterdam Clinical Epidemiology and Biostatistics The Netherlands

Assistance Publique Hôpitaux de Paris

ATS Sardegna ASL 3 Nuoro Nuoro Italy

ATS Sardegna ASSL Nuoro Ospedale San Francesco Nuoro Italy

Bart's Heart Centre St Bartholomew's Hospital London

Cardiology Centre Institute for Clinical and Experimental Medicine Prague Czech Republic

Cardiology Department Parma University Hospital Italy

Cardiology Division Department of Internal Medicine University of Utah Salt Lake City

Cardiovascular Division Department of Medicine Washington University School of Medicine Saint Louis MO

Cardiovascular Research Center Center for Human Genetic Research Massachusetts General Hospital Boston

Cardiovascular Research Institute National University of Singapore

Cardiovascular Research School Erasmus Medical Center

Centre de recherche de l'Institut Universitaire de cardiologie et de pneumologie de Québec Canada

Centre for Experimental Medicine Institute for Clinical and Experimental Medicine Prague Czech Republic

Centre for Genomic Health Queen Mary University of London United Kingdom

Centre for Outcomes Research and Evaluation Research Institute of the McGill University Health Centre Montreal QC Canada

Centro de Pesquisa Clinica Hospital Universitario Universidade de Sao Paulo São Paulo Brazil

Clinica Mediterranea Naples Italy

Clinical Institute of Medical and Chemical Laboratory Diagnostics Medical University of Graz Austria

Clinical Trial Service Unit and Epidemiological Studies Unit Nuffield Department of Population Health Medical Research Council Population Health Research Unit University of Oxford United Kingdom

CNR Institute of Clinical Physiology Pisa

Department of Anesthesia Critical Care and Pain Medicine Beth Israel Deaconess Medical Center Boston MA

Department of Anesthesiology Perioperative and Pain Medicine Brigham and Women's Hospital Boston MA

Department of Biochemistry Microbiology and Immunology University of Ottawa ON Canada

Department of Biomedical Informatics Emory Clinical Cardiovascular Research Institute Emory University School of Medicine Atlanta GA

Department of Biomedical Informatics University of Utah Salt Lake City

Department of Biomedical Sciences Humanitas University Milan Italy

Department of Biostatistics and Epidemiology Texas Heart Institute Houston

Department of Cardio Thoracic Surgery Finnish Cardiovascular Research Center Faculty of Medicine and Life Sciences University of Tampere Finland

Department of Cardio Thoracic Surgery Heart Centre Tampere University Hospital Finland

Department of Cardio Thoracic Surgery University of Tampere Finland

Department of Cardiology and Internal Diseases Military Institute of Medicine Warsaw Poland

Department of Cardiology Clinical Sciences Lund University Skåne University Hospital

Department of Cardiology Erasmus MC Thoraxcenter

Department of Cardiology Heart Center Tampere University Hospital Finland

Department of Cardiology Herlev and Gentofte Hospital Hellerup Denmark

Department of Cardiology Leiden University Medical Centre the Netherlands

Department of Cardiology Medical University of Bialystok Poland

Department of Cardiology The Heart Centre Copenhagen University Hospital Rigshospitalet

Department of Cardiology University of Lund Sweden

Department of Cardiology University of Tampere Finland

Department of Cardiology Uppsala Clinical Research Centre Uppsala University Sweden

Department of Cardiovascular Medicine Centre for Microbiome and Human Health Heart and Vascular Institute Cleveland Clinic OH

Department of Cardiovascular Medicine Heart and Vascular Institute and Centre for Clinical Genomics Cleveland Clinic OH

Department of Cardiovascular Medicine Humanitas Clinical and Research Centre Milan Italy

Department of Cardiovascular Medicine University of Münster Germany

Department of Cardiovascular Sciences BHF Cardiovascular Research Centre University of Leicester United Kingdom

Department of Cardiovascular Sciences Katholieke Universiteit Leuven Belgium

Department of Cellular and Molecular Medicine Lerner Research Institute Cleveland Clinic OH

Department of Clinical Biochemistry Copenhagen University Hospital Gentofte

Department of Clinical Chemistry and Hematology UMC Utrecht the Netherlands

Department of Clinical Chemistry Fimlab Laboratories Tampere Finland

Department of Clinical Chemistry UMC Utrecht the Netherlands

Department of Clinical Chemistry University of Tampere Finland

Department of Clinical Physiology Tampere University Hospital Finland

Department of Clinical Physiology University of Tampere Finland

Department of Clinical Sciences Lund University Malmö Sweden

Department of Epidemiology Emory University Rollins School of Public Health Atlanta GA

Department of Forensic Medicine Faculty of Medical Sciences University of Copenhagen Denmark

Department of Forensic Medicine; Medical University of Bialystok

Department of Health Sciences University of Leicester United Kingdom

Department of Internal Medicine Jagiellonian University Medical College Kraków Poland

Department of Internal Medicine Skåne University Hospital Malmö Sweden

Department of Medical Genetics Medical University of Warsaw Poland

Department of Medicine and Cardiology Academic Teaching Hospital Feldkirch Austria

Department of Medicine Faculty of Medicine Université Laval QC Canada

Department of Medicine McGill University Health Centre Montreal QC Canada

Department of Medicine University of Verona Italy

Department of Neurology and Neurosurgery Brain Centre Rudolf Magnus and Julius Centre for Health Sciences and Primary Care UMC Utrecht Utrecht University the Netherlands

Department of Pathology and Molecular Medicine McMaster University

Department of Pharmacotherapy and Translational Research Centre for Pharmacogenomics University of Florida Gainesville

Department of Population Medicine and Civilization Disease Prevention Medical University of Bialystok Poland

Department of Respiratory Medicine Academic Medical Centre University of Amsterdam

Department of Vascular Medicine Academic Medical Centre Amsterdam

Department of Vascular Medicine UMC Utrecht Utrecht University the Netherlands

Departments of Medicine and Biochemistry Microbiology and Immunology University of Ottawa ON Canada

Departments of Preventive Medicine and Biochemistry and Molecular Medicine Keck School of Medicine of USC Los Angeles CA

Division Heart and Lungs Department of Cardiology UMC Utrecht University of Utrecht the Netherlands

Division Laboratories Pharmacy and Biomedical Genetics Laboratory of Clinical Chemistry and Hematology UMC Utrecht Utrecht University the Netherlands

Division of Cardiology Department of Medical Sciences Uppsala University Sweden

Division of Cardiology Department of Medicine Emory Clinical Cardiovascular Research Institute Emory University School of Medicine Atlanta GA

Division of Cardiology Department of Medicine Royal Victoria Hospital McGill Univ Health Centre Montreal QC Canada

Division of Cardiovascular Medicine College of Medicine University of Florida Gainesville

Division of Clinical Chemistry Department of Medical Sciences Uppsala University Sweden

Division of Clinical Epidemiology and Aging Research German Cancer Research Center

Division of Heart and Lungs Department of Cardiology UMC Utrecht the Netherlands

Division of Molecular and Clinical Medicine School of Medicine University of Dundee Scotland United Kingdom

Division of Pharmacoepidemiology and Clinical Pharmacology Utrecht University the Netherlands

Drexel University College of Medicine Philadelphia PA

Durrer Centre of Cardiogenetic Research ICIN Netherlands Heart Institute Utrecht

Einthoven Laboratory for Experimental Vascular Medicine LUMC Leiden

Estonian Genome Centre Department of Biotechnology Institute of Genomics Institute of Molecular and Cell Biology University of Tartu Estonia

Faculty of Medicine Université de Montréal QC Canada

first Chair and Department of Cardiology Medical University of Warsaw Poland

Harvard Medical School Boston MA

Heart and Lung Centre Helsinki University Hospital and University of Helsinki Finland

Heart Centre Leipzig Germany

Heart Health Research Group University of Auckland New Zealand

Heart Institute University of Sao Paulo Brazil

Institute for Biomedicine Eurac Research Affiliated Institute of the University of Lübeck Bolzano Italy

Institute for Genetic Medicine Keck School of Medicine of USC Los Angeles CA

Institute for Medical Informatics Statistics and Epidemiology University of Leipzig Germany

Institute of Cardiovascular and Medical Sciences University of Glasgow United Kingdom

Institute of Cardiovascular Science Faculty of Population Health Science University College London United Kingdom

Institute of Clinical Chemistry and Laboratory Medicine University Hospital Regensburg Germany

Institute of Environmental Medicine Karolinska Institute Stockholm Sweden

Institute of Health Informatics Faculty of Population Health Science University College London United Kingdom

Institute of Laboratory Medicine Clinical Chemistry and Molecular Diagnostics University Hospital Leipzig Germany

Intermountain Heart Institute Intermountain Medical Center Salt Lake City UT

Interuniversity Cardiology Institute of the Netherlands Utrecht

Julius Center for Health Sciences and Primary Care UMC Utrecht Utrecht University the Netherlands

Laboratory for Translational Genetics Department of Human Genetics Katholieke Universiteit Leuven Belgium

Laboratory for Translational Genetics VIB Center for Cancer Biology Belgium

Laboratory of Experimental Cardiology UMC Utrecht the Netherlands

Laval University Institute universitaire de cardiologie et de pneumologie de Québec Canada

LIFE Research Centre for Civilization Diseases University of Leipzig Germany

Medical Central Laboratories Feldkirch Austria

Montreal Heart Institute OC Canada

National Heart and Lung Institute Imperial College and Institute of Cardiovascular Medicine and Science Royal Brompton Hospital London United Kingdom

National Institute for Health Research Oxford Biomedical Research Centre Oxford University Hospital United Kingdom

Network Aging Research

NIHR Leicester Biomedical Research Centre Glenfield Hospital United Kingdom

Paris Sorbonne University UPMC Site St Antoine France

Pat Macpherson Centre for Pharmacogenetics and Pharmacogenomics Division of Molecular and Clinical Medicine Ninewells Hospital and Medical School Dundee

Population Health Research Institute Hamilton ON Canada

Preventive and Genomic Cardiology McGill University Health Centre Montreal QC Canada

Princess Al Jawhara Al Brahim Centre of Excellence in Research of Hereditary Disorders Jeddah Saudi Arabia

Private University of the Principality of Liechtenstein Triesen

Program in Medical and Population Genetics Broad Institute Cambridge MA

QMRI Cardiovascular Sciences University of Edinburgh United Kingdom

Research Institute of the McGill University Health Centre Montreal QC Canada

Respiratory Oncology Unit Department of Respiratory Medicine University Hospitals KU Leuven Belgium

Robertson Centre for Biostatistics University of Glasgow United Kingdom

Ruddy Canadian Cardiovascular Genetics Centre University of Ottawa Heart Institute ON Canada

Saint Luke's Mid America Heart Insti Kansas City MO

Saint Luke's Mid America Heart Institute University of Missouri Kansas City

Section of Cardiology Michael E DeBakey Veterans Affairs Medical Center Houston TX

Section of Cardiovascular Research Department of Medicine Baylor College of Medicine Houston TX

Section of Gerontology and Geriatrics Department of Internal Medicine Leiden University Medical Centre the Netherlands

St Antonius Hospital Department Cardiology Nieuwegein the Netherlands

Statistical Genomics Division Department of Genetics Washington University School of Medicine Saint Louis MO

Synlab Academy Synlab Holding Deutschland GmbH Mannheim Germany

The Christchurch Heart Institute University of Otago Christchurch New Zealand

The University of Edinburgh United Kingdom

Transplantation Laboratory Helsinki University Hospital and University of Helsinki Finland

Unit of Epidemiology and Biostatistics Department of Health Science and Technology Aalborg University Hospital Denmark

Université Paris Descartes France

University Medical Centre University of Groningen the Netherlands

University of Texas School of Public Health Houston

Uppsala Clinical Research Center Sweden

Vorarlberg Institute for Vascular Investigation and Treatment

Wallenberg Centre for Molecular Medicine Lund University Diabetes Centre Lund University Sweden

William Harvey Research Institute Barts and the London Medical School Queen Mary University of London United Kingdom

Zobrazit více v PubMed

Ford ES, et al. Proportion of the decline in cardiovascular mortality disease due to prevention versus treatment: public health versus clinical care. Annu Rev Public Health. 2011;32:5–22. doi: 10.1146/annurev-publhealth-031210-101211. PubMed

Sidney S, et al. Recent trends in cardiovascular mortality in the united states and public health goals. JAMA Cardiol. 2016;1:594–599. doi: 10.1001/jamacardio.2016.1326. PubMed

Ford ES, et al. Explaining the decrease in U.S. deaths from coronary disease, 1980-2000. N Engl J Med. 2007;356:2388–2398. doi: 10.1056/NEJMsa053935. PubMed

Benjamin EJ, et al. American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2017 Update: a report from the American Heart Association. Circulation. 2017;135:e146–e603. doi: 10.1161/CIR.0000000000000485. PubMed PMC

Scarborough PBP, et al. Coronary Heart Disease Statistics 2010 Edition. London: British Heart Foundation; 2010.

Yusuf S, et al. Interheart Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364:937–952. doi: 10.1016/S0140-6736(04)17018-9. PubMed

Deloukas P, et al. Large-scale association analysis identifies new risk loci for coronary artery disease. Nat Genet. 2013;45:25–33. PubMed PMC

Fox KA, et al. Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE). BMJ. 2006;333:1091. doi: 10.1136/bmj.38985.646481.55. PubMed PMC

Schiele F, et al. Coronary artery disease: risk stratification and patient selection for more aggressive secondary prevention. Eur J Prev Cardiol. 2017;24(3_suppl):88–100. doi: 10.1177/2047487317706586. PubMed

Schwartz GG, et al. dal-OUTCOMES Investigators. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med. 2012;367:2089–2099. doi: 10.1056/NEJMoa1206797. PubMed

White HD, et al. Darapladib for preventing ischemic events in stable coronary heart disease. N Engl J Med. 2014;370:1702–1711. PubMed

Boden WE, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365:2255–2267. PubMed

Armitage JM, et al. Effects of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and major morbidity in myocardial infarction survivors: a randomized trial. JAMA. 2010;303:2486–2494. PubMed

Global BMIMC, et al. Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents. Lancet. 2016;388:776–786. PubMed PMC

Wang ZJ, et al. Association of body mass index with mortality and cardiovascular events for patients with coronary artery disease: a systematic review and meta-analysis. Heart. 2015;101:1631–1638. doi: 10.1136/heartjnl-2014-307119. PubMed

Cannon CP, et al. Improve-IT Investigators. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372:2387–2397. doi: 10.1056/NEJMoa1410489. PubMed

Sabatine MS, et al. Fourier Steering Committee and Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376:1713–1722. doi: 10.1056/NEJMoa1615664. PubMed

Ridker PM, et al. Cantos Trial Group. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377:1119–1131. doi: 10.1056/NEJMoa1707914. PubMed

Patel RS, et al. The Genius-CHD consortium. Eur Heart J. 2015;36:2674–2676. PubMed

Rothman KJ, Greenland S Modern epidemiology. 2nd ed. Philadelphia: Lippincott-Raven; 1998.

Lee JC, et al. UK IBD Genetics Consortium. Genome-wide association study identifies distinct genetic contributions to prognosis and susceptibility in Crohn’s disease. Nat Genet. 2017;49:262–268. doi: 10.1038/ng.3755. PubMed PMC

Ohman EM, et al. Reach Registry Investigators. The Reduction of Atherothrombosis for Continued Health (REACH) registry: an international, prospective, observational investigation in subjects at risk for atherothrombotic events-study design. Am Heart J. 2006;151:786.e1–786.e. doi: 10.1016/j.ahj.2005.11.004. PubMed

Psaty BM, et al. The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium as a model of collaborative science. Epidemiology. 2013;24:346–348. doi: 10.1097/EDE.0b013e31828b2cbb. PubMed

Collins R, et al. What makes UK Biobank special? Lancet. 2012;379:1173–1174. doi: 10.1016/S0140-6736(12)60404-8. PubMed

Chen Z, et al. China Kadoorie Biobank (CKB) collaborative group. China Kadoorie Biobank of 0.5 million people: survey methods, baseline characteristics and long-term follow-up. Int J Epidemiol. 2011;40:1652–1666. doi: 10.1093/ije/dyr120. PubMed PMC

Reilly MP, et al. Myocardial Infarction Genetics Consortium; Wellcome Trust Case Control Consortium. Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies. Lancet. 2011;377:383–392. doi: 10.1016/S0140-6736(10)61996-4. PubMed PMC

Dahabreh IJ, et al. Index event bias as an explanation for the paradoxes of recurrence risk research. JAMA. 2011;305:822–823. doi: 10.1001/jama.2011.163. PubMed PMC

Nicholls SJ, et al. Effect of evolocumab on progression of coronary disease in statin-treated patients: the glagov randomized clinical trial. JAMA. 2016;316:2373–2384. doi: 10.1001/jama.2016.16951. PubMed

Hu YJ, et al. Impact of selection bias on estimation of subsequent event risk. Circ Cardiovasc Genet. 2017;10:001616. PubMed PMC

Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events