Association of a Genetic Risk Score with Prevalent and Incident Myocardial Infarction in Subjects Undergoing Coronary Angiography

• Type of Material: Article
• Authors: Riyaz S. Patel, Emory University; Yan Sun, Emory University; Jaana Hartiala, University of Southern California, Los Angeles; Emir Veledar, Emory University; Shaoyong Su, Emory University; Salman Sher, Emory University; Ying Liu, Emory University; Ayaz M. Rahman, Emory University; Ronak Patel, Emory University; Syed Tanveer Rab, Emory University; Viola Vaccarino, Emory University; A. Maziar Zafari, Emory University; Habib Samady, Emory University; W.H. Wilson Tang, Cleveland Clinic; Hooman Allayee, University of Southern California, Los Angeles; Stanley L. Hazen, Cleveland Clinic; Arshed Ali Quyyumi, Emory University
• Language: English
• Date: 2012-08-01
• Publisher: American Heart Association
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2011 American Heart Association, Inc.
• Final Published Version (URL): http://circgenetics.ahajournals.org/content/5/4/441
• Title of Journal or Parent Work: Circulation: Cardiovascular Genetics
• ISSN: 1942-325X
• Volume: 5
• Issue: 4
• Start Page: 441
• End Page: 449
• Grant/Funding Information: Emory: This work was supported by the American Heart Association (Postdoctoral Fellowship for RSP), National Institutes of Health R01 HL89650-01, Robert W. Woodruff Health Sciences Center Fund, Emory Heart and Vascular Center Funds and supported in part by NIH Grant UL1 RR025008 from the Clinical and Translational Science Award program and NIH grant R24HL085343. Cleveland Clinic: GeneBank has been supported by National Institutes of Health grants P01HL087018-020001, P01HL076491-055328, 1R01HL103866, 1RO1HL103931, and the Cleveland Clinic Clinical Research Unit of the Case Western Reserve University CTSA (1UL1RR024989). SLH has also been supported in part by a grant from the LeDucq Foundation, and a gift from the Leonard Kreiger Fund.
• Keywords: myocardial infarction; Genetic Risk Score; coronary artery disease; cardiovascular disease risk factors
• Research Categories: Health Sciences, Epidemiology; Biology, Genetics; Health Sciences, Medicine and Surgery

Abstract

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 old without prior MI, and followed them for incident MI and death. Genotyping was performed for 11 established CAD/MI variants and a GRS 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 years, compared to older controls (≥70 years) 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 c-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 non-significant 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 two independent angiographic cohorts. These findings have implications for understanding the clinical utility of genetic risk scores for secondary as opposed to primary risk prediction.