Journal
CIRCULATION-GENOMIC AND PRECISION MEDICINE
Volume 12, Issue 4, Pages -Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCGEN.119.002471
Keywords
chromosome; genetic; variation; myocardial infarction; risk factor; secondary prevention
Funding
- British Heart Foundation Intermediate Fellowship [FS/14/76/30933]
- National Institute for Health Research University College London Hospitals Biomedical Research Centre
- UK Medical Research Council
- British Heart Foundation Intermediate Clinical Research Fellowship [FS/18/23/33512]
- National Institute for Health Research Oxford Biomedical Research Centre
- Netherlands Heart Foundation [2001D019, 2003T302, 2007B202, CVON 2012-10]
- Leducq Foundation [05-CVD]
- Center for Translational Molecular Medicine
- NIH (National Institutes of Health) [R0133169, R01ES021801, R01MD010358, R01ES025786, R01HL103866, R01DK106000, R01HL126827, P20HL113452, P01HL098055, P01HL076491, R01HL103931]
- NIHR
- Barts Charity
- Aarno Koskelo Foundation
- Helsinki University Central Hospital special government funds [TYH7215, TKK2012005, TYH2012209, TYH2014312]
- Finnish Foundation for Cardiovascular research
- National Heart Long and Blood Institute [A. Fox/R01 HL 098601]
- Heart Foundation of New Zealand
- National Institutes of Health/National Institutes of Aging [AG051633]
- Abraham J. AMP
- Phyllis Katz Foundation (Atlanta, GA)
- NIH [5P01HL101398-02, 1P20HL113451-01, 1R56HL126558-01, 1RF-1AG051633-01, R01 NS064162-01, R01 HL89650-01, HL095479-01, 1U10HL110302-01, 1DP3DK094346-01, 2P01HL086773-06A1]
- EU [692145]
- Estonian Research Council [IUT20-60, IUT24-6, PUT1660, PUT735]
- European Union [01KL1802, 2014-2020.4.01.15-0012]
- ERA-CVD grant Detectin-Heart failure [2R01DK075787-06A1]
- Canadian Institutes of Health Research
- Nova Scotia, Ontario
- Quebec (HSFC)
- Wellcome Trust [072960/Z/03/Z, 084726/Z/08/Z, 084727/Z/08/Z, 085475/Z/08/Z, 085475/B/08/Z]
- EU IMI-SUMMIT programme
- NHS Education of Scotland/Chief Scientist Office Postdoctoral Clinical Lectureship [PCL 17/07]
- Italian Ministry of Research's Fund for Basic Research
- Sanofi Aventis
- Chief Scientist Office, Scotland
- National Institute of Health Pharmacogenomics Research Network grant [U01-GM074492, R01 HL074730]
- University of Florida Opportunity Fund
- BASF Pharma
- German Ministry of Education and Research [01GD9820/0, 01ER0814]
- Willy-Robert-Pitzer Foundation
- Waldburg-Zeil Clinics Isny
- Polish Ministry of Science and Higher Education [NN402083939]
- National Science Centre [2013/09/B/NZ5/00770]
- Leipzig Research Center for Civilization Diseases (LIFE)
- European Union
- European Regional Development Fund (ERDF)
- Free State of Saxony
- Seventh Framework Program [201668]
- European Research Council Advanced Grant [294609]
- Italian Ministry of Health [PE-2013-02356818]
- Italian Ministry of Education, University and Research [2015583WMX]
- University of Ottawa Heart Institute
- Heart and Stroke Foundation
- Established Clinical Investigator of the Netherlands Heart Foundation [2001 D 032]
- European commission [223004]
- Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging) [050-060-810]
- FRSQ
- Merck Frost Canada
- Pfizer Canada
- Swedish Council for Work Life and Social Research
- Stockholm County Council
- Genome Canada
- Genome Quebec
- Canadian Institutes of Health Research (CIHR)
- Fonds de recherche du Quebec-Sante (FRQS)
- National Institutes of Health [Cresci R01 NR013396]
- National Institutes of Health: Washington University School of Medicine SCCOR [P50 HL077113]
- Dutch Top Institute Pharma Mondriaan Project
- Cariverona Foundation
- Veneto Region
- Italian Ministry of Education, University, and Research (MIUR)
- LURM (Laboratorio Universitario di Ricerca Medica) Research Center, University of Verona
- National Centre for Research and Development (NCBiR) [N R13 0001 06]
- Medical University of Warsaw
- British Heart Foundation
- University College London Hospitals NIHR Biomedical Research Centre
- EU/EF-PIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart grant [116074]
- European Union's Horizon 2020 research and innovation programme under the ERA-NET Co-fund action [01KL1802]
- BHF [PG/18/5033837]
- Health Research Council
- Heart and Stroke Foundation of Alberta, NWT AMP
- Nunavut, British Columbia and Yukon
- Heart and Stroke Foundation of NWT Nunavut
- Heart and Stroke Foundation of British Columbia
- Heart and Stroke Foundation of Yukon
- Institute of Clinical and Experimental Medicine, Prague [00023001]
- Wellcome Trust
- Abbott Laboratories
- Epidemiologia e Genetica della Morte Improvvisa in Sardegna
- National Science Center (Poland) [N N 402 529139]
- Bristol Myers Squibb USA
- HSFC
- Pfizer
- Netherlands Heart Foundation
- European Research Council (ERC) [294609] Funding Source: European Research Council (ERC)
Ask authors/readers for more resources
BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk. METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD. RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09). CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
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