國家衛生研究院 NHRI:Item 3990099045/11287
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    题名: Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries
    作者: Zekavat, SM;Ruotsalainen, S;Handsaker, RE;Alver, M;Bloom, J;Poterba, T;Seed, C;Ernst, J;Chaffin, M;Engreitz, J;Peloso, GM;Manichaikul, A;Yang, C;Ryan, KA;Fu, M;Johnson, WC;Tsai, M;Budoff, M;Ramachandran, VS;Cupples, LA;Rotter, JI;Rich, SS;Post, W;Mitchell, BD;Correa, A;Metspalu, A;Wilson, JG;Salomaa, V;Kellis, M;Daly, MJ;Neale, BM;McCarroll, S;Surakka, I;Esko, T;Ganna, A;Ripatti, S;Kathiresan, S;Natarajan, P;Damcott, C, .;Hsiung, CA;et al.
    贡献者: Institute of Population Health Sciences
    摘要: 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.
    日期: 2018-12
    關聯: Nature Communications. 2018 Dec;9:Article number 2606.
    Link to: http://dx.doi.org/10.1038/s41467-018-04668-w
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2041-1723&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000437252300006
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85049751193
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