Genomic prediction of coronary heart disease

被引:236
作者
Abraham, Gad [1 ,2 ]
Havulinna, Aki S. [3 ]
Bhalala, Oneil G. [1 ,2 ]
Byars, Sean G. [1 ,2 ]
De Livera, Alysha M. [1 ,2 ,4 ]
Yetukuri, Laxman [5 ]
Tikkanen, Emmi [5 ]
Perola, Markus [3 ,5 ]
Schunkert, Heribert [6 ,7 ,8 ]
Sijbrands, Eric J. [9 ]
Palotie, Aarno [5 ,10 ,11 ,12 ]
Samani, Nilesh J. [13 ,14 ]
Salomaa, Veikko [3 ]
Ripatti, Samuli [5 ,15 ,16 ]
Inouye, Michael [1 ,2 ,5 ]
机构
[1] Univ Melbourne, Sch BioSci, Ctr Syst Genom, Parkville, Vic 3010, Australia
[2] Univ Melbourne, Dept Pathol, Parkville, Vic 3010, Australia
[3] Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland
[4] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Parkville, Vic 3010, Australia
[5] Univ Helsinki, FIMM, FI-00014 Helsinki, Finland
[6] Deutsch Herzzentrum Munich, D-80636 Munich, Germany
[7] Tech Univ Munich, D-80636 Munich, Germany
[8] DZHK, Partner Site Munich Heart Alliance, D-81377 Munich, Germany
[9] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands
[10] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA
[11] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA
[12] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA
[13] Univ Leicester, Glenfield Hosp, BHF Cardiovasc Res Ctr, Dept Cardiovasc Sci, Groby Rd, Leicester LE3 9QP, Leics, England
[14] Glenfield Hosp, Leicester Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, Groby Rd, Leicester LE3 9QP, Leics, England
[15] Wellcome Trust Res Labs, Wellcome Trust Sanger Inst, Genome Campus, Cambridge CB10 1SA, England
[16] Univ Helsinki, Dept Publ Hlth, FI-00014 Helsinki, Finland
基金
芬兰科学院; 英国惠康基金; 英国医学研究理事会; 美国国家卫生研究院;
关键词
Genomic risk score; Coronary heart disease; Myocardial infarction; Framingham risk score; Primary prevention; GENETIC RISK SCORE; CARDIOVASCULAR-DISEASE; EVENTS; POLYMORPHISMS; ASSOCIATION;
D O I
10.1093/eurheartj/ehw450
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aims Genetics plays an important role in coronary heart disease (CHD) but the clinical utility of genomic risk scores (GRSs) relative to clinical risk scores, such as the Framingham Risk Score (FRS), is unclear. Our aim was to construct and externally validate a CHD GRS, in terms of lifetime CHD risk and relative to traditional clinical risk scores. Methods and results We generated a GRS of 49 310 SNPs based on a CARDIoGRAMplusC4D Consortium meta-analysis of CHD, then independently tested it using five prospective population cohorts (three FINRISK cohorts, combined n = 12 676, 757 incident CHD events; two Framingham Heart Study cohorts (FHS), combined n = 3406, 587 incident CHD events). The GRS was associated with incident CHD (FINRISK HR = 1.74, 95% confidence interval (CI) 1.61-1.86 per S.D. of GRS; Framingham HR = 1.28, 95% CI 1.18-1.38), and was largely unchanged by adjustment for known risk factors, including family history. Integration of the GRS with the FRS or ACC/AHA13 scores improved the 10 years risk prediction (meta-analysis C-index: +1.5-1.6%, P < 0.001), particularly for individuals >= 60 years old (meta-analysis C-index: +4.6-5.1%, P < 0.001). Importantly, the GRS captured substantially different trajectories of absolute risk, with men in the top 20% of attaining 10% cumulative CHD risk 12-18 y earlier than those in the bottom 20%. High genomic risk was partially compensated for by low systolic blood pressure, low cholesterol level, and non-smoking. Conclusions A GRS based on a large number of SNPs improves CHD risk prediction and encodes different trajectories of lifetime risk not captured by traditional clinical risk scores.
引用
收藏
页码:3267 / 3278
页数:12
相关论文
共 34 条
[1]   Accurate and Robust Genomic Prediction of Celiac Disease Using Statistical Learning [J].
Abraham, Gad ;
Tye-Din, Jason A. ;
Bhalala, Oneil G. ;
Kowalczyk, Adam ;
Zobel, Justin ;
Inouye, Michael .
PLOS GENETICS, 2014, 10 (02)
[2]   Performance and Robustness of Penalized and Unpenalized Methods for Genetic Prediction of Complex Human Disease [J].
Abraham, Gad ;
Kowalczyk, Adam ;
Zobel, Justin ;
Inouye, Michael .
GENETIC EPIDEMIOLOGY, 2013, 37 (02) :184-195
[3]   A global reference for human genetic variation [J].
Altshuler, David M. ;
Durbin, Richard M. ;
Abecasis, Goncalo R. ;
Bentley, David R. ;
Chakravarti, Aravinda ;
Clark, Andrew G. ;
Donnelly, Peter ;
Eichler, Evan E. ;
Flicek, Paul ;
Gabriel, Stacey B. ;
Gibbs, Richard A. ;
Green, Eric D. ;
Hurles, Matthew E. ;
Knoppers, Bartha M. ;
Korbel, Jan O. ;
Lander, Eric S. ;
Lee, Charles ;
Lehrach, Hans ;
Mardis, Elaine R. ;
Marth, Gabor T. ;
McVean, Gil A. ;
Nickerson, Deborah A. ;
Wang, Jun ;
Wilson, Richard K. ;
Boerwinkle, Eric ;
Doddapaneni, Harsha ;
Han, Yi ;
Korchina, Viktoriya ;
Kovar, Christie ;
Lee, Sandra ;
Muzny, Donna ;
Reid, Jeffrey G. ;
Zhu, Yiming ;
Chang, Yuqi ;
Feng, Qiang ;
Fang, Xiaodong ;
Guo, Xiaosen ;
Jian, Min ;
Jiang, Hui ;
Jin, Xin ;
Lan, Tianming ;
Li, Guoqing ;
Li, Jingxiang ;
Li, Yingrui ;
Liu, Shengmao ;
Liu, Xiao ;
Lu, Yao ;
Ma, Xuedi ;
Tang, Meifang ;
Wang, Bo .
NATURE, 2015, 526 (7571) :68-+
[4]   Lifetime Risks of Cardiovascular Disease [J].
Berry, Jarett D. ;
Dyer, Alan ;
Cai, Xuan ;
Garside, Daniel B. ;
Ning, Hongyan ;
Thomas, Avis ;
Greenland, Philip ;
Van Horn, Linda ;
Tracy, Russell P. ;
Lloyd-Jones, Donald M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (04) :321-329
[5]   Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls [J].
Burton, Paul R. ;
Clayton, David G. ;
Cardon, Lon R. ;
Craddock, Nick ;
Deloukas, Panos ;
Duncanson, Audrey ;
Kwiatkowski, Dominic P. ;
McCarthy, Mark I. ;
Ouwehand, Willem H. ;
Samani, Nilesh J. ;
Todd, John A. ;
Donnelly, Peter ;
Barrett, Jeffrey C. ;
Davison, Dan ;
Easton, Doug ;
Evans, David ;
Leung, Hin-Tak ;
Marchini, Jonathan L. ;
Morris, Andrew P. ;
Spencer, Chris C. A. ;
Tobin, Martin D. ;
Attwood, Antony P. ;
Boorman, James P. ;
Cant, Barbara ;
Everson, Ursula ;
Hussey, Judith M. ;
Jolley, Jennifer D. ;
Knight, Alexandra S. ;
Koch, Kerstin ;
Meech, Elizabeth ;
Nutland, Sarah ;
Prowse, Christopher V. ;
Stevens, Helen E. ;
Taylor, Niall C. ;
Walters, Graham R. ;
Walker, Neil M. ;
Watkins, Nicholas A. ;
Winzer, Thilo ;
Jones, Richard W. ;
McArdle, Wendy L. ;
Ring, Susan M. ;
Strachan, David P. ;
Pembrey, Marcus ;
Breen, Gerome ;
St Clair, David ;
Caesar, Sian ;
Gordon-Smith, Katherine ;
Jones, Lisa ;
Fraser, Christine ;
Green, Elain K. .
NATURE, 2007, 447 (7145) :661-678
[6]   Large-scale association analysis identifies new risk loci for coronary artery disease [J].
Deloukas, Panos ;
Kanoni, Stavroula ;
Willenborg, Christina ;
Farrall, Martin ;
Assimes, Themistocles L. ;
Thompson, John R. ;
Ingelsson, Erik ;
Saleheen, Danish ;
Erdmann, Jeanette ;
Goldstein, Benjamin A. ;
Stirrups, Kathleen ;
Koenig, Inke R. ;
Cazier, Jean-Baptiste ;
Johansson, Asa ;
Hall, Alistair S. ;
Lee, Jong-Young ;
Willer, Cristen J. ;
Chambers, John C. ;
Esko, Tonu ;
Folkersen, Lasse ;
Goel, Anuj ;
Grundberg, Elin ;
Havulinna, Aki S. ;
Ho, Weang K. ;
Hopewell, Jemma C. ;
Eriksson, Niclas ;
Kleber, Marcus E. ;
Kristiansson, Kati ;
Lundmark, Per ;
Lyytikainen, Leo-Pekka ;
Rafelt, Suzanne ;
Shungin, Dmitry ;
Strawbridge, Rona J. ;
Thorleifsson, Gudmar ;
Tikkanen, Emmi ;
Van Zuydam, Natalie ;
Voight, Benjamin F. ;
Waite, Lindsay L. ;
Zhang, Weihua ;
Ziegler, Andreas ;
Absher, Devin ;
Altshuler, David ;
Balmforth, Anthony J. ;
Barroso, Ines ;
Braund, Peter S. ;
Burgdorf, Christof ;
Claudi-Boehm, Simone ;
Cox, David ;
Dimitriou, Maria ;
Do, Ron .
NATURE GENETICS, 2013, 45 (01) :25-U52
[7]   Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) [J].
Cleeman, JI ;
Grundy, SM ;
Becker, D ;
Clark, LT ;
Cooper, RS ;
Denke, MA ;
Howard, WJ ;
Hunninghake, DB ;
Illingworth, DR ;
Luepker, RV ;
McBride, P ;
McKenney, JM ;
Pasternak, RC ;
Stone, NJ ;
Van Horn, L ;
Brewer, HB ;
Ernst, ND ;
Gordon, D ;
Levy, D ;
Rifkind, B ;
Rossouw, JE ;
Savage, P ;
Haffner, SM ;
Orloff, DG ;
Proschan, MA ;
Schwartz, JS ;
Sempos, CT ;
Shero, ST ;
Murray, EZ .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2001, 285 (19) :2486-2497
[8]   AN APPROACH TO LONGITUDINAL STUDIES IN A COMMUNITY - FRAMINGHAM STUDY [J].
DAWBER, TR ;
KANNEL, WB ;
LYELL, LP .
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1963, 107 (02) :539-&
[9]   Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium [J].
Dehghan, Abbas ;
Bis, Joshua C. ;
White, Charles C. ;
Smith, Albert Vernon ;
Morrison, Alanna C. ;
Cupples, L. Adrienne ;
Trompet, Stella ;
Chasman, Daniel I. ;
Lumley, Thomas ;
Voelker, Uwe ;
Buckley, Brendan M. ;
Ding, Jingzhong ;
Jensen, Majken K. ;
Folsom, Aaron R. ;
Kritchevsky, Stephen B. ;
Girman, Cynthia J. ;
Ford, Ian ;
Doerr, Marcus ;
Salomaa, Veikko ;
Uitterlinden, Andre G. ;
Eiriksdottir, Gudny ;
Vasan, Ramachandran S. ;
Franceschini, Nora ;
Carty, Cara L. ;
Virtamo, Jarmo ;
Demissie, Serkalem ;
Amouyel, Philippe ;
Arveiler, Dominique ;
Heckbert, Susan R. ;
Ferrieres, Jean ;
Ducimetiere, Pierre ;
Smith, Nicholas L. ;
Wang, Ying A. ;
Siscovick, David S. ;
Rice, Kenneth M. ;
Wiklund, Per-Gunnar ;
Taylor, Kent D. ;
Evans, Alun ;
Kee, Frank ;
Rotter, Jerome I. ;
Karvanen, Juha ;
Kuulasmaa, Kari ;
Heiss, Gerardo ;
Kraft, Peter ;
Launer, Lenore J. ;
Hofman, Albert ;
Markus, Marcello R. P. ;
Rose, Lynda M. ;
Silander, Kaisa ;
Wagner, Peter .
PLOS ONE, 2016, 11 (03)
[10]   FRAMINGHAM OFFSPRING STUDY - DESIGN AND PRELIMINARY DATA [J].
FEINLEIB, M ;
KANNEL, WB ;
GARRISON, RJ ;
MCNAMARA, PM ;
CASTELLI, WP .
PREVENTIVE MEDICINE, 1975, 4 (04) :518-525