Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans.
Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans.
复制标题
与人类血液低密度脂蛋白胆固醇、高密度脂蛋白胆固醇或甘油三酯相关的六个新位点。
DOI：
10.1038/ng.75
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发表时间：
2008-02
期刊：
影响因子：
30.8
通讯作者：
Orho-Melander, Marju
中科院分区：
文献类型：
--
作者：
Kathiresan, Sekar;Melander, Olle;Guiducci, Candace;Surti, Aarti;Burtt, Noel P.;Rieder, Mark J.;Cooper, Gregory M.;Roos, Charlotta;Voight, Benjamin F.;Havulinna, Aki S.;Wahlstrand, Bjorn;Hedner, Thomas;Corella, Dolores;Tai, E. Shyong;Ordovas, Jose M.;Berglund, Goran;Vartiainen, Erkki;Jousilahti, Pekka;Hedblad, Bo;Taskinen, Marja-Riitta;Newton-Cheh, Christopher;Salomaa, Veikko;Peltonen, Leena;Groop, Leif;Altshuler, David M.;Orho-Melander, Marju
血液中脂蛋白和脂质浓度是心血管疾病的遗传危险因素。使用来自三项研究的全基因组关联数据（n = 8,816，包括2,758名来自糖尿病遗传学倡议的个体，以及1,874名来自2型糖尿病的FUSION研究的个体和4,184名来自SardiNIA研究的衰老相关变量的个体，该研究在本期的配套论文中报道），以及多达18,554名独立参与者的靶向复制关联分析，我们发现18个位点上的常见snp与低密度脂蛋白（LDL）胆固醇、高密度脂蛋白（HDL）胆固醇和/或甘油三酯的浓度具有可重复性相关。这些基因座中有6个是新的（每个新基因座的P < 5 × 10−8）。在新发现的6个染色体区域中，2个与LDL胆固醇相关（1p13靠近CELSR2、PSRC1和SORT1, 19p13靠近CILP2和PBX4）， 1个与HDL胆固醇相关（1q42位于GALNT2）， 5个与甘油三酯相关（7q11位于TBL2和MLXIPL附近，8q24位于TRIB1附近，1q42位于GALNT2, 19p13位于CILP2和PBX4附近，1p31位于ANGPTL3附近）。在1p13位点，低密度脂蛋白相关SNP也与人类肝脏中CELSR2、PSRC1和SORT1转录水平密切相关，并且该SNP的代理最近被证明影响冠状动脉疾病的风险。了解新发现的基因座的分子、细胞和临床后果可以为治疗和临床护理提供信息。
Blood concentrations of lipoproteins and lipids are heritable risk factors for cardiovascular disease. 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) 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 × 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. Understanding the molecular, cellular and clinical consequences of the newly identified loci may inform therapy and clinical care.
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DOI：
10.1056/nejmoa072366
发表时间：
2007-08-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Samani NJ;Erdmann J;Hall AS;Hengstenberg C;Mangino M;Mayer B;Dixon RJ;Meitinger T;Braund P;Wichmann HE;Barrett JH;König IR;Stevens SE;Szymczak S;Tregouet DA;Iles MM;Pahlke F;Pollard H;Lieb W;Cambien F;Fischer M;Ouwehand W;Blankenberg S;Balmforth AJ;Baessler A;Ball SG;Strom TM;Braenne I;Gieger C;Deloukas P;Tobin MD;Ziegler A;Thompson JR;Schunkert H;WTCCC and the Cardiogenics Consortium
通讯作者：
WTCCC and the Cardiogenics Consortium
影响因子：
2.1
作者：
NAMBOODIRI K K;KAPLAN E B;RIFKIND B M
通讯作者：
RIFKIND B M
影响因子：
64.5
作者：
KINGSLEY, DM;KOZARSKY, KF;KRIEGER, M
通讯作者：
KRIEGER, M
影响因子：
3.5
作者：
Knoblauch, H;Bauerfeind, A;Reich, JG
通讯作者：
Reich, JG
影响因子：
168.9
作者：
Hansson, L;Hedner, T;Karlberg, BE
通讯作者：
Karlberg, BE