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

doi:10.1038/s41467-019-11541-x

GSTDTAP > 资源环境科学

DOI	10.1038/s41467-019-11541-x
	Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries
	Zekavat, Seyedeh M.1,2,3; Ruotsalainen, Sanni 4; Handsaker, Robert E.1,5,6; Alver, Maris 8,9; Bloom, Jonathan 1,7; Poterba, Timothy 1,7; Seed, Cotton 1,7; Ernst, Jason 10; Chaffin, Mark 1; Engreitz, Jesse 1; Peloso, Gina M.11; Manichaikul, Ani 12; Yang, Chaojie 12; Ryan, Kathleen A.13; Fu, Mao 13; Johnson, W. Craig 14; Tsai, Michael 15; Budoff, Matthew 16; Ramachandran, Vasan S.17,18,19,20,21,22,23,24,25; Cupples, L. Adrienne 11,17; Rotter, Jerome I.26,27; Rich, Stephen S.12; Post, Wendy 28; Mitchell, Braxton D.29; Correa, Adolfo 30; Metspalu, Andres 9; Wilson, James G.30; Salomaa, Veikko 31; Kellis, Manolis 1,32; Daly, Mark J.1,5,7; Neale, Benjamin M.1,5,7; McCarroll, Steven 1,5,6; Surakka, Ida 4; Esko, Tonu 1,9; Ganna, Andrea 1,5,7; Ripatti, Samuli 1,4,33; Kathiresan, Sekar 1,34,35,36; Natarajan, Pradeep 1,34,35,36
	2019-09-20
发表期刊	NATURE COMMUNICATIONS
ISSN	2041-1723
出版年	2018
卷号	9
文章类型	Article
语种	英语
国家	USA; Finland; Estonia
英文摘要	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.
领域	资源环境
收录类别	SCI-E
WOS记录号	WOS:000437252300006
WOS关键词	CORONARY-HEART-DISEASE ; WIDE ASSOCIATION ; GENETIC-VARIANTS ; CARDIOVASCULAR-DISEASE ; COMPONENTS-ANALYSIS ; POPULATION-SCALE ; RARE VARIANTS ; LOW-FREQUENCY ; RISK-FACTOR ; CHOLESTEROL
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
URL	查看原文
引用统计	被引频次：80[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/204553
专题	资源环境科学
作者单位	1.Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA; 2.Yale Sch Med, New Haven, CT 06510 USA; 3.Yale Univ, Dept Computat Biol & Bioinformat, New Haven, CT 06510 USA; 4.Univ Helsinki, Inst Mol Med, Helsinki, Finland; 5.Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA; 6.Harvard Med Sch, Dept Genet, Boston, MA 02115 USA; 7.Analyt & Translat Genet Unit, Boston, MA 02142 USA; 8.Univ Tartu, Inst Mol & Cell Biol, Dept Biotechnol, Tartu, Estonia; 9.Estonian Genome Ctr, Tallinn, Estonia; 10.Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA; 11.Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA; 12.Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22904 USA; 13.Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Program Personalized & Genom Med,Dept Med, Baltimore, MD 21201 USA; 14.Univ Washington, Sch Publ Hlth & Community Med, Dept Biostat, Seattle, WA 98195 USA; 15.Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA; 16.Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Div Cardiol, Los Angeles, CA 90509 USA; 17.NHLBI, Framingham Heart Study, Bldg 10, Bethesda, MD 20892 USA; 18.Boston Univ, Sch Med, Dept Med, Sect Prevent Med & Epidemiol, Boston, MA 02118 USA; 19.Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA; 20.Boston Univ, Sch Med, Dept Epidemiol, Sect Prevent Med & Epidemiol, Boston, MA 02118 USA; 21.Boston Univ, Sch Med, Dept Epidemiol, Sect Cardiovasc Med, Boston, MA 02118 USA; 22.Boston Univ, Sch Publ Hlth, Dept Med, Sect Prevent Med & Epidemiol, Boston, MA 02118 USA; 23.Boston Univ, Sch Publ Hlth, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA; 24.Boston Univ, Sch Publ Hlth, Dept Epidemiol, Sect Prevent Med & Epidemiol, Boston, MA 02118 USA; 25.Boston Univ, Sch Publ Hlth, Dept Epidemiol, Sect Cardiovasc Med, Boston, MA 02118 USA; 26.Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Dept Pediat, Torrance, CA 90509 USA; 27.Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Dept Med, Torrance, CA 90509 USA; 28.Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA; 29.Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA; 30.Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA; 31.Natl Inst Hlth & Welf, Helsinki, Finland; 32.MIT, Comp Sci & Artificial Intelligence Lab, 32 Vassar St, Cambridge, MA 02139 USA; 33.Univ Helsinki, Dept Publ Hlth, Fac Med, Helsinki, Finland; 34.Harvard Med Sch, Dept Med, Boston, MA 02115 USA; 35.Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA; 36.Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA
推荐引用方式 GB/T 7714	Zekavat, Seyedeh M.,Ruotsalainen, Sanni,Handsaker, Robert E.,et al. Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries[J]. NATURE COMMUNICATIONS,2019,9.
APA	Zekavat, Seyedeh M..,Ruotsalainen, Sanni.,Handsaker, Robert E..,Alver, Maris.,Bloom, Jonathan.,...&Natarajan, Pradeep.(2019).Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries.NATURE COMMUNICATIONS,9.
MLA	Zekavat, Seyedeh M.,et al."Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries".NATURE COMMUNICATIONS 9(2019).