期刊
CIRCULATION-CARDIOVASCULAR GENETICS
卷 5, 期 4, 页码 441-449出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCGENETICS.111.960229
关键词
cardiovascular disease risk factors; coronary artery disease; myocardial infarction; genetic risk score
资金
- American Heart Association (Postdoctoral Fellowship for RSP)
- National Institutes of Health [R01 HL89650-01, P01HL087018-020001, P01HL076491-055328, 1R01HL103866, 1RO1HL103931]
- Robert W. Woodruff Health Sciences Center Fund
- Emory Heart and Vascular Center Funds
- NIH Grant from the Clinical and Translational Science Award program [UL1 RR025008]
- NIH grant [R24HL085343]
- Cleveland Clinic Clinical Research Unit of the Case Western Reserve University CTSA [1UL1RR024989]
- LeDucq Foundation
- Abbott Laboratories
- Cleveland HeartLab Inc
- Esperion Therapeutics Inc
- LipoScience Inc.
- National Institute for Health Research [CL-2011-11-003] Funding Source: researchfish
Background-Genome-wide association studies have identified multiple variants associating with coronary artery disease (CAD) and myocardial infarction (MI). Whether a combined genetic risk score (GRS) is associated with prevalent and incident MI in high-risk subjects remains to be established. Methods and Results-In subjects undergoing cardiac catheterization (n=2597), we identified cases with a history of MI onset at age <70 years and controls >= 70 years without prior MI and followed them for incident MI and death. Genotyping was performed for 11 established CAD/MI variants, and a GRS was calculated based on average number of risk alleles carried at each locus weighted by effect size. Replication of association findings was sought in an independent angiographic cohort (n=2702). The GRS was significantly associated with prevalent MI, occurring before age 70, compared with older controls (>= 70 years of age) with no history of MI (P<0.001). This association was successfully replicated in a second cohort, yielding a pooled P value of <0.001. The GRS modestly improved the area-under-the-curve statistic in models of prevalent MI with traditional risk factors; however, the association was not statistically significant when elderly controls without MI but with stable angiographic CAD were examined (pooled P=0.11). Finally, during a median 2.5-year follow-up, only a nonsignificant trend was noted between the GRS and incident events, which was also not significant in the replication cohort. Conclusions-A GRS of 11 CAD/MI variants is associated with prevalent MI but not near-term incident adverse events in 2 independent angiographic cohorts. These findings have implications for understanding the clinical use of genetic risk scores for secondary as opposed to primary risk prediction. (Circ Cardiovasc Genet. 2012;5:441-449.)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据