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Effect of 9p21 genetic variation on coronary heart disease is not modified by other risk markers. The Atherosclerosis Risk in Communities (ARIC) Study

  • Aaron R. Folsom
    Correspondence
    Corresponding author. Tel.: +1 612 626 8862; fax: +1 612 624 0315.
    Affiliations
    Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, 1300 South 2nd Street, Suite 300, Minneapolis, MN 55454, USA
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  • Vijay Nambi
    Affiliations
    Division of Atherosclerosis and Vascular Medicine, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA

    Center for Cardiovascular Prevention, Methodist DeBakey Heart and Vascular Center, 6565 Fannin St., Suite STE B 160, Room MS-A601, Houston, TX 77030, USA
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  • James S. Pankow
    Affiliations
    Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, 1300 South 2nd Street, Suite 300, Minneapolis, MN 55454, USA
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  • Weihong Tang
    Affiliations
    Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, 1300 South 2nd Street, Suite 300, Minneapolis, MN 55454, USA
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  • Kian Farbakhsh
    Affiliations
    Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, 1300 South 2nd Street, Suite 300, Minneapolis, MN 55454, USA
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  • Kazumasa Yamagishi
    Affiliations
    Department of Public Health Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan
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  • Eric Boerwinkle
    Affiliations
    Human Genetics Center, University of Texas Health Science Center, School of Public Health, 1200 Herman Pressler Drive, Houston, TX 77030, USA
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      Abstract

      Objective

      To determine whether the 9p21 SNP association with coronary heart disease is modified by other classical or novel risk markers.

      Methods

      The 9p21 SNP (rs10757274) and multiple risk markers were measured in the Atherosclerosis Risk in Communities Study, and incident coronary disease events were ascertained. Effect modification (interaction) of the 9p21 SNP with risk markers was tested in Cox proportional hazard regression models.

      Results

      The incidence rates of coronary heart disease per 1000 person-years were 14.4, 17.0, and 18.7 for AA, AG, and GG genotypes, yielding hazard ratios of 1.0, 1.20 (95% CI = 1.07–1.36), and 1.34 (95% CI = 1.16–1.53). There was no meaningful evidence of an interaction (all p-interaction > 0.04) between 9p21 SNP and any of 14 other risk markers for coronary heart disease. These included novel markers not previously explored for 9p21 interaction (e.g., cardiac troponin T and N-terminal pro-brain natriuretic peptide).

      Conclusion

      Our study extends evidence that the 9p21 SNP association with coronary heart disease is not modified by classical or novel risk markers. Our findings therefore rule out additional plausible pathways by which 9p21 might have increased coronary heart disease risk.

      Highlights

      • Other risk markers may modify the association between 9p21 and coronary disease.
      • We tested 14 classical or novel risk markers, and found no meaningful interactions.
      • Our study is one of the largest conducted to date on this topic.

      Keywords

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