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    Bivariate genetic association of KIAA1797 with heart rate in American Indians: The Strong Heart Family Study

    Access Status
    Open access via publisher
    Authors
    Melton, P.
    Rutherford, S.
    Voruganti, V.
    Göring, H.
    Laston, S.
    Haack, K.
    Comuzzie, A.
    Dyer, T.
    Johnson, M.
    Kent, J.
    Curran, J.
    Moses, Eric
    Blangero, J.
    Barac, A.
    Lee, E.
    Best, L.
    Fabsitz, R.
    Devereux, R.
    Okin, P.
    Bella, J.
    Broeckel, U.
    Howard, B.
    MacCluer, J.
    Cole, S.
    Almasy, L.
    Date
    2010
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Melton, P. and Rutherford, S. and Voruganti, V. and Göring, H. and Laston, S. and Haack, K. and Comuzzie, A. et al. 2010. Bivariate genetic association of KIAA1797 with heart rate in American Indians: The Strong Heart Family Study. Human Molecular Genetics. 19 (18): pp. 3662-3671.
    Source Title
    Human Molecular Genetics
    DOI
    10.1093/hmg/ddq274
    ISSN
    0964-6906
    School
    School of Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/45768
    Collection
    • Curtin Research Publications
    Abstract

    Heart rate (HR) has been identified as a risk factor for cardiovascular disease (CVD), yet little is known regarding genetic factors influencing this phenotype. Previous research in American Indians (AIs) from the Strong Heart Family Study (SHFS) identified a significant quantitative trait locus (QTL) for HR on chromosome 9p21. Genetic association on HR was conducted in the SHFS. HR was measured from electrocardiogram (ECG) and echocardiograph (Echo) Doppler recordings. We examined 2248 single-nucleotide polymorphisms (SNPs) on chromosome 9p21 for association using a gene-centric statistical test. We replicated the aforementioned QTL [logarithm of odds (LOD) = 4.83; genome-wide P = 0.0003] on chromosome 9p21 in one SHFS population using joint linkage of ECG and Echo HR. After correcting for effective number of SNPs using a gene-centric test, six SNPs (rs7875153, rs7848524, rs4446809, rs10964759, rs1125488 and rs7853123) remained significant. We applied a novel bivariate association method, which was a joint test of association of a single locus to two traits using a standard additive genetic model. The SNP, rs7875153, provided the strongest evidence for association (P = 7.14 × 10-6). This SNP (rs7875153) is rare (minor allele frequency = 0.02) in AIs and is located within intron 9 of the gene KIAA1797. To support this association, we applied lymphocyte RNA expression data from the San Antonio Family Heart Study, a longitudinal study of CVD in Mexican Americans. Expression levels of KIAA1797 were significantly associated (P = 0.012) with HR. These findings in independent populations support that KIAA1797 genetic variation may be associated with HR but elucidation of a functional relationship requires additional study. © The Author 2010. Published by Oxford University Press. All rights reserved.

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