Genotype-informed estimation of risk of coronary heart disease based on genome-wide association data linked to the electronic medical record

BMC Cardiovascular Disorders

Research Article

Kent R Bailey¹  Keyue Ding²  Iftikhar J Kullo² 

[1] Division of Biomedical Informatics and Statistics, Mayo Clinic, 55905, Rochester, MN, USA;Division of Cardiovascular Diseases, Mayo Clinic, 55905, Rochester, MN, USA;

关键词: Coronary Heart Disease;    Risk Allele;    Coronary Heart Disease Risk;    Framingham Risk Score;    Genetic Risk Score;   

DOI  :  10.1186/1471-2261-11-66

 received in 2011-01-05, accepted in 2011-11-03,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundSusceptibility variants identified by genome-wide association studies (GWAS) have modest effect sizes. Whether such variants provide incremental information in assessing risk for common 'complex' diseases is unclear. We investigated whether measured and imputed genotypes from a GWAS dataset linked to the electronic medical record alter estimates of coronary heart disease (CHD) risk.MethodsStudy participants (n = 1243) had no known cardiovascular disease and were considered to be at high, intermediate, or low 10-year risk of CHD based on the Framingham risk score (FRS) which includes age, sex, total and HDL cholesterol, blood pressure, diabetes, and smoking status. Of twelve SNPs identified in prior GWAS to be associated with CHD, four were genotyped in the participants as part of a GWAS. Genotypes for seven SNPs were imputed from HapMap CEU population using the program MACH. We calculated a multiplex genetic risk score for each patient based on the odds ratios of the susceptibility SNPs and incorporated this into the FRS.ResultsThe mean (SD) number of risk alleles was 12.31 (1.95), range 6-18. The mean (SD) of the weighted genetic risk score was 12.64 (2.05), range 5.75-18.20. The CHD genetic risk score was not correlated with the FRS (P = 0.78). After incorporating the genetic risk score into the FRS, a total of 380 individuals (30.6%) were reclassified into higher-(188) or lower-risk groups (192).ConclusionA genetic risk score based on measured/imputed genotypes at 11 susceptibility SNPs, led to significant reclassification in the 10-y CHD risk categories. Additional prospective studies are needed to assess accuracy and clinical utility of such reclassification.

【 授权许可】

Unknown   
© Ding et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.