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    Pleiotropy of cardiometabolic syndrome with obesity-related anthropometric traits determined using empirically derived kinships from the Busselton Health Study

    Access Status
    Fulltext not available
    Authors
    Cadby, G.
    Melton, P.
    McCarthy, N.
    Almeida, M.
    Williams-Blangero, S.
    Curran, J.
    VandeBerg, J.
    Hui, J.
    Beilby, J.
    Musk, A.
    James, A.
    Hung, J.
    Blangero, J.
    Moses, Eric
    Date
    2017
    Type
    Journal Article
    
    Metadata
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    Citation
    Cadby, G. and Melton, P. and McCarthy, N. and Almeida, M. and Williams-Blangero, S. and Curran, J. and VandeBerg, J. et al. 2017. Pleiotropy of cardiometabolic syndrome with obesity-related anthropometric traits determined using empirically derived kinships from the Busselton Health Study. Human Genetics. 137 (1): pp. 45–53.
    Source Title
    Human Genetics
    DOI
    10.1007/s00439-017-1856-x
    ISSN
    0340-6717
    School
    School of Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/59507
    Collection
    • Curtin Research Publications
    Abstract

    Over two billion adults are overweight or obese and therefore at an increased risk of cardiometabolic syndrome (CMS). Obesity-related anthropometric traits genetically correlated with CMS may provide insight into CMS aetiology. The aim of this study was to utilise an empirically derived genetic relatedness matrix to calculate heritabilities and genetic correlations between CMS and anthropometric traits to determine whether they share genetic risk factors (pleiotropy). We used genome-wide single nucleotide polymorphism (SNP) data on 4671 Busselton Health Study participants. Exploiting both known and unknown relatedness, empirical kinship probabilities were estimated using these SNP data. General linear mixed models implemented in SOLAR were used to estimate narrow-sense heritabilities (h 2 ) and genetic correlations (r g ) between 15 anthropometric and 9 CMS traits. Anthropometric traits were adjusted by body mass index (BMI) to determine whether the observed genetic correlation was independent of obesity. After adjustment for multiple testing, all CMS and anthropometric traits were significantly heritable (h 2 range 0.18–0.57). We identified 50 significant genetic correlations (r g range: - 0.37 to 0.75) between CMS and anthropometric traits. Five genetic correlations remained significant after adjustment for BMI [high density lipoprotein cholesterol (HDL-C) and waist–hip ratio; triglycerides and waist–hip ratio; triglycerides and waist–height ratio; non-HDL-C and waist–height ratio; insulin and iliac skinfold thickness]. This study provides evidence for the presence of potentially pleiotropic genes that affect both anthropometric and CMS traits, independently of obesity.

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