American Journal of Epidemiology Advance Access originally published online on April 18, 2007
American Journal of Epidemiology 2007 166(1):28-35; doi:10.1093/aje/kwm060
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ORIGINAL CONTRIBUTIONS |
Prediction of Coronary Heart Disease Risk using a Genetic Risk Score: The Atherosclerosis Risk in Communities Study
1 Human Genetics Center and Division of Epidemiology, University of Texas Health Science Center at Houston, Houston, TX
2 Celera, Alameda, CA
3 Collaborative Studies Coordinating Center, University of North Carolina, Chapel Hill, NC
4 Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, Cleveland, OH
5 Cardiovascular Research Institute, University of California, San Francisco, CA
6 Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN
7 Texas Heart Institute, Houston, TX
Correspondence to Dr. Eric Boerwinkle, Human Genetics Center, University of Texas Health Science Center at Houston, 1200 Herman Pressler, Suite 453E, Houston, TX 77030 (e-mail: Eric.Boerwinkle{at}uth.tmc.edu).
Received for publication May 4, 2006. Accepted for publication January 16, 2007.
Recent studies have evaluated whether incorporating nontraditional risk factors improves coronary heart disease (CHD) prediction models. This 1986–2001 US study aggregated the contribution of multiple single nucleotide polymorphisms into a genetic risk score (GRS) and assessed whether the GRS plus traditional risk factors predict CHD better than traditional risk factors alone. The Atherosclerosis Risk in Communities (ARIC) cohort was followed for a median of 13 years for CHD events (n = 1,452). Individuals were genotyped for 116 single nucleotide polymorphisms associated with CHD in multiple case-control studies. Single nucleotide polymorphisms nominally predicting incident CHD in the ARIC study were included in the GRS. The GRS was significantly associated with incident CHD in Blacks (hazard rate ratio = 1.20, 95% confidence interval: 1.11, 1.29) and Whites (hazard rate ratio = 1.10, 95% confidence interval: 1.06, 1.14) as well as in each tertile defined by the traditional cardiovascular risk score (p 
0.02). When receiver operating characteristic curves based on traditional risk factors were recalculated after the GRS was added, the increase in the area under the receiver operating characteristic curve was statistically significant for Blacks and suggestive of improved CHD prediction for Whites. This study demonstrates the concept of aggregating information from multiple single nucleotide polymorphisms into a risk score and indicates that it can improve prediction of incident CHD in the ARIC study.
cardiovascular diseases; genetics; polymorphism, genetic; risk factors
Abbreviations: ACRS, ARIC Cardiovascular Risk Score; ARIC, Atherosclerosis Risk in Communities; AUC, area under the curve; CHD, coronary heart disease; GRS, genetic risk score; SNP, single nucleotide polymorphism
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