Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries
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2018Journal
Nature CommunicationsPublisher
Nature Publishing GroupType
Article
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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/s41467-020-15236-6Identifier 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/10713/9806ae974a485f413a2113503eed53cd6c53
10.1038/s41467-018-04668-w
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