Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans

被引：1108
|
作者：
Kathiresan, Sekar [1 ,2 ,3 ,4 ]
Melander, Olle [5 ]
Guiducci, Candace [2 ,3 ]
Surti, Aarti [2 ,3 ]
Burtt, Noel P. [2 ,3 ]
Rieder, Mark J. [6 ]
Cooper, Gregory M. [6 ]
Roos, Charlotta [7 ]
Voight, Benjamin F. [2 ,3 ,8 ,9 ]
Havulinna, Aki S. [10 ]
Wahlstrand, Bjorn [11 ]
Hedner, Thomas [11 ]
Corella, Dolores [12 ]
Tai, E. Shyong [13 ]
Ordovas, Jose M. [14 ]
Berglund, Goran [15 ]
Vartiainen, Erkki [10 ]
Jousilahti, Pekka [10 ]
Hedblad, Bo [16 ]
Taskinen, Marja-Riitta [17 ]
Newton-Cheh, Christopher [1 ,2 ,3 ,4 ]
Salomaa, Veikko [10 ]
Peltonen, Leena [2 ,3 ,10 ,18 ,19 ]
Groop, Leif [7 ,20 ]
Altshuler, David M. [2 ,3 ,4 ,8 ,9 ,21 ]
Orho-Melander, Marju [7 ]
机构：
[1] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA
[2] MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA
[3] Harvard Univ, Cambridge, MA 02142 USA
[4] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA
[5] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Hypertens & Cardiovasc Dis, S-20502 Malmo, Sweden
[6] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA
[7] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Diabet & Endocrinol, S-20502 Malmo, Sweden
[8] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA
[9] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA
[10] Natl Publ Hlth Inst, SF-00300 Helsinki, Finland
[11] Sahlgrens Univ Hosp, Dept Clin Pharmacol, S-41345 Gothenburg, Sweden
[12] Univ Valencia, Sch Med, Dept Prevent Med, Valencia 46010, Spain
[13] Singapore Gen Hosp, Dept Endocrinol, Singapore 169608, Singapore
[14] Tufts Univ, Nutr & Genom Lab, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA 02111 USA
[15] Lund Univ, Malmo Univ Hosp, Dept Internal Med, S-20502 Malmo, Sweden
[16] Lund Univ, Malmo Univ Hosp, Dept Epidemiol Res, S-20502 Malmo, Sweden
[17] Univ Helsinki, Dept Med, Helsinki 00029, Finland
[18] Univ Helsinki, Dept Med Genet, Helsinki 00029, Finland
[19] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England
[20] Helsinki Univ Hosp, Dept Med, Helsinki 00029, Finland
[21] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA
来源：
NATURE GENETICS | 2008年 / 40卷 / 02期
基金：
英国惠康基金;
关键词：
D O I：
10.1038/ng.75
中图分类号：
Q3 [遗传学];
学科分类号：
071007 ; 090102 ;
摘要：
Blood concentrations of lipoproteins and lipids are heritable(1) risk factors for cardiovascular disease(2,3). Using genome-wide association data from three studies (n = 8,816 that included 2,758 individuals from the Diabetes Genetics Initiative specific to the current paper as well as 1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables reported in a companion paper in this issue(4)) and targeted replication association analyses in up to 18,554 independent participants, we show that common SNPs at 18 loci are reproducibly associated with concentrations of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and/or triglycerides. Six of these loci are new (P < 5 x 10(-8) for each new locus). Of the six newly identified chromosomal regions, two were associated with LDL cholesterol (1p13 near CELSR2, PSRC1 and SORT1 and 19p13 near CILP2 and PBX4), one with HDL cholesterol (1q42 in GALNT2) and five with triglycerides (7q11 near TBL2 and MLXIPL, 8q24 near TRIB1, 1q42 in GALNT2, 19p13 near CILP2 and PBX4 and 1p31 near ANGPTL3). At 1p13, the LDL-associated SNP was also strongly correlated with CELSR2, PSRC1, and SORT1 transcript levels in human liver, and a proxy for this SNP was recently shown to affect risk for coronary artery disease(5). Understanding the molecular, cellular and clinical consequences of the newly identified loci may inform therapy and clinical care.
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页码：189 / 197
页数：9
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