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    Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries

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    Author
    Zekavat, S.M.
    Ruotsalainen, S.
    Handsaker, R.E.
    Date
    2018
    Journal
    Nature Communications
    Publisher
    Nature Publishing Group
    Type
    Article
    
    Metadata
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    See at
    https://dx.doi.org/10.1038/s41467-018-04668-w
    https://doi.org/10.1038/s41467-020-15236-6
    Abstract
    Lipoprotein(a), Lp(a), is a modified low-density lipoprotein particle that contains apolipoprotein(a), encoded by LPA, and is a highly heritable, causal risk factor for cardiovascular diseases that varies in concentrations across ancestries. Here, we use deep-coverage whole genome sequencing in 8392 individuals of European and African ancestry to discover and interpret both single-nucleotide variants and copy number (CN) variation associated with Lp(a). We observe that genetic determinants between Europeans and Africans have several unique determinants. The common variant rs12740374 associated with Lp(a) cholesterol is an eQTL for SORT1 and independent of LDL cholesterol. Observed associations of aggregates of rare non-coding variants are largely explained by LPA structural variation, namely the LPA kringle IV 2 (KIV2)-CN. Finally, we find that LPA risk genotypes confer greater relative risk for incident atherosclerotic cardiovascular diseases compared to directly measured Lp(a), and are significantly associated with measures of subclinical atherosclerosis in African Americans. Copyright 2018 The Author(s).
    Description
    An amendment to this paper has been published and can be accessed at https://doi.org/10.1038/s41467-020-15236-6
    Keyword
    Lipoprotein(a)
    Lipoproteins
    Lp(a) level
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85049751193&doi=10.1038%2fs41467-018-04668-w&partnerID=40&md5=b27b75fbe701b4c1c152a3b6ff6d4b21; http://hdl.handle.net/10713/9806
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41467-018-04668-w
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    UMB Open Access Articles 2018

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