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  • Admixture Mapping of Coronary Artery Calcified Plaque in African Americans With Type 2 Diabetes Mellitus

    Author(s)
    Divers, Jasmin
    D. Palmer, Nicholette
    Lu, Lingyi
    Register, Thomas C.
    Carr, J. Jeffrey
    Hicks, Pamela J.
    Caresse Hightower, R.
    Carrie Smith, S.
    Xu, Jianzhao
    Cox, Amanda J.
    A. Hruska, Keith
    Bowden, Donald W.
    E. Lewis, Cora
    Heiss, Gerardo
    A. Province, Michael
    B. Borecki, Ingrid
    F. Kerr, Kathleen
    Ida Chen, Y.
    Palmas, Walter
    I. Rotter, Jerome
    L. Wassel, Christina
    Bertoni, Alain G.
    Herrington, David M.
    E. Wagenknecht, Lynne
    Langefeld, Carl D.
    Freedman, Barry I.
    Griffith University Author(s)
    Cox, Amanda J.
    Year published
    2013
    Metadata
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    Abstract
    Background-The presence and severity of coronary artery calcified plaque (CAC) differs markedly between individuals of African and European descent, suggesting that admixture mapping may be informative for identifying genetic variants associated with subclinical cardiovascular disease. Methods and Results-Admixture mapping of CAC was performed in 1040 unrelated African Americans with type 2 diabetes mellitus from the African American-Diabetes Heart Study, Multi-Ethnic Study of Atherosclerosis and Family Heart Study using the Illumina custom ancestry informative marker panel. All cohorts obtained computed tomography scanning ...
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    Background-The presence and severity of coronary artery calcified plaque (CAC) differs markedly between individuals of African and European descent, suggesting that admixture mapping may be informative for identifying genetic variants associated with subclinical cardiovascular disease. Methods and Results-Admixture mapping of CAC was performed in 1040 unrelated African Americans with type 2 diabetes mellitus from the African American-Diabetes Heart Study, Multi-Ethnic Study of Atherosclerosis and Family Heart Study using the Illumina custom ancestry informative marker panel. All cohorts obtained computed tomography scanning of the coronary arteries using identical protocols. For each ancestry informative marker, the probability of inheriting 0, 1, and 2 copies of a European-derived allele was determined. Linkage analysis was performed by testing for association between each ancestry informative marker using these probabilities and CAC, accounting for global ancestry, age, sex, and study. Markers on 1p32.3 in the GLIS1 gene (rs6663966, logarithm of odds [LOD]=3.7), 1q32.1 near CHIT1 (rs7530895, LOD=3.1), 4q21.2 near PRKG2 (rs1212373, LOD=3.0), and 11q25 in the OPCML gene (rs6590705, LOD=3.4) had statistically significant LOD scores, whereas markers on 8q22.2 (rs6994682, LOD=2.7), 9p21.2 (rs439314, LOD=2.7), and 13p32.1 (rs7492028, LOD=2.8) manifested suggestive evidence of linkage. These regions were uniformly characterized by higher levels of European ancestry associating with higher levels or odds of CAC. Findings were replicated in 1350 African Americans without diabetes mellitus and 2497 diabetic European Americans from Multi-Ethnic Study of Atherosclerosis and the Diabetes Heart Study. Conclusions-Fine mapping these regions will likely identify novel genetic variants that contribute to CAC and clarify racial differences in susceptibility to subclinical cardiovascular disease.
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    Journal Title
    Circulation: Cardiovascular Genetics
    Volume
    6
    DOI
    https://doi.org/10.1161/CIRCGENETICS.112.964114
    Subject
    Cardiorespiratory Medicine and Haematology not elsewhere classified
    Genetics
    Medical Biotechnology
    Cardiorespiratory Medicine and Haematology
    Publication URI
    http://hdl.handle.net/10072/61481
    Collection
    • Journal articles

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