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    GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

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    Author
    Franceschini, N.
    Giambartolomei, C.
    de Vries, P.S.
    Date
    2018
    Journal
    Nature Communications
    Publisher
    Nature Publishing Group
    Type
    Article
    
    Metadata
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    See at
    https://dx.doi.org/10.1038/s41467-018-07340-5
    Abstract
    Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans. Copyright 2018, The Author(s).
    Keyword
    Genome-Wide Association Study
    Polymorphism, Single Nucleotide
    expression quantitative
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85057617727&doi=10.1038%2fs41467-018-07340-5&partnerID=40&md5=18dd837b5cdba434106f353e5246c10e; http://hdl.handle.net/10713/9803
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41467-018-07340-5
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