Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts.
Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts.
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DOI：
10.1038/ng.269
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发表时间：
2009-01
期刊：
影响因子：
30.8
通讯作者：
Peltonen, Leena
中科院分区：
文献类型：
--
作者：
Aulchenko, Yurii S.;Ripatti, Samuli;Lindqvist, Ida;Boomsma, Dorret;Heid, Iris M.;Pramstaller, Peter P.;Penninx, Brenda W. J. H.;Janssens, A. Cecile J. W.;Wilson, James F.;Spector, Tim;Martin, Nicholas G.;Pedersen, Nancy L.;Kyvik, Kirsten Ohm;Kaprio, Jaakko;Hofman, Albert;Freimer, Nelson B.;Jarvelin, Marjo-Riitta;Gyllensten, Ulf;Campbell, Harry;Rudan, Igor;Johansson, Asa;Marroni, Fabio;Hayward, Caroline;Vitart, Veronique;Jonasson, Inger;Pattaro, Cristian;Wright, Alan;Hastie, Nick;Pichler, Irene;Hicks, Andrew A.;Falchi, Mario;Willemsen, Gonneke;Hottenga, Jouke-Jan;de Geus, Eco J. C.;Montgomery, Grant W.;Whitfield, John;Magnusson, Patrik;Saharinen, Juha;Perola, Markus;Silander, Kaisa;Isaacs, Aaron;Sijbrands, Eric J. G.;Uitterlinden, Andre G.;Witteman, Jacqueline C. M.;Oostra, Ben A.;Elliott, Paul;Ruokonen, Aimo;Sabatti, Chiara;Gieger, Christian;Meitinger, Thomas;Kronenberg, Florian;Doering, Angela;Wichmann, H-Erich;Smit, Johannes H.;McCarthy, Mark I.;van Duijn, Cornelia M.;Peltonen, Leena
最近的脂质全基因组关联（GWA）研究已在确定其他表型，特别是糖尿病的样本中进行。在这里，我们报告了影响总胆固醇（TC），低密度脂蛋白（LDL）胆固醇，高密度脂蛋白（HDL）胆固醇和甘油三酯的基因座的第一次GWA分析，这些基因座从16个基于人群的队列中随机抽样，并主要使用Illumina HumanHap 300-Duo平台进行基因分型。我们的研究共包括17，797 - 22，562人，年龄在18-104岁之间，地理区域从北欧国家到南欧。我们建立了22个与血脂水平相关的基因座，在全基因组显著性水平（P < 5 × 10-8），其中包括16个基因座已被确定为以前的GWA研究。在我们的队列样本中新鉴定的六个基因座是ABCG 5（TC，P = 1.5 × 10 ~（-11）;低密度脂蛋白，P = 2.6 × 10-10），TMEM 57（TC，P = 5.4 × 10-10），CTCF-PRMT 8区域（HDL，P = 8.3 × 10-16）、DNAH11（LDL，P = 6.1 × 10-9）、FADS3-FADS2（TC，P = 1.5 × 10-10; LDL，P = 4.4 × 10-13）和MADD-FOLH1区（HDL，P = 6 × 10-11）。对于三个位点，效应量显着不同性别。基于脂质位点的遗传风险评分可解释高达4.8%的脂质变异，并且还与内膜中层厚度增加（P = 0.001）和冠心病发病率增加（P = 0.04）相关。遗传风险评分改善了对血脂异常高危人群的筛查，优于经典风险因素。
Recent genome-wide association (GWA) studies of lipids have been conducted in samples ascertained for other phenotypes, particularly diabetes. Here we report the first GWA analysis of loci affecting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform. Our study included a total of 17,797-22,562 persons, aged 18-104 years and from geographic regions spanning from the Nordic countries to Southern Europe. We established 22 loci associated with serum lipid levels at a genome-wide significance level (P < 5 × 10-8), including 16 loci that were identified by previous GWA studies. The six newly identified loci in our cohort samples are ABCG5 (TC, P = 1.5 × 10-11; LDL, P = 2.6 × 10-10), TMEM57 (TC, P = 5.4 × 10-10), CTCF-PRMT8 region (HDL, P = 8.3 × 10-16), DNAH11 (LDL, P = 6.1 × 10-9), FADS3-FADS2 (TC, P = 1.5 × 10-10; LDL, P = 4.4 × 10-13) and MADD-FOLH1 region (HDL, P = 6 × 10-11). For three loci, effect sizes differed significantly by sex. Genetic risk scores based on lipid loci explain up to 4.8% of variation in lipids and were also associated with increased intima media thickness (P = 0.001) and coronary heart disease incidence (P = 0.04). The genetic risk score improves the screening of high-risk groups of dyslipidemia over classical risk factors.
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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。
影响因子：
30.8
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
通讯作者：
Orho-Melander, Marju
影响因子：
--
作者：
Pattaro, Cristian;Marroni, Fabio;Pramstaller, Peter P.
通讯作者：
Pramstaller, Peter P.
影响因子：
9.8
作者：
Friedlander, Y;Austin, MA;King, MC
通讯作者：
King, MC
影响因子：
3.5
作者：
Janssens, A. Cecile J. W.;van Duijn, Cornelia M.
通讯作者：
van Duijn, Cornelia M.
DOI：
10.1016/s0889-8529(03)00073-2
发表时间：
2003-12-01
影响因子：
4.5
作者：
Howard, BV;Ruotolo, G;Robbins, DC
通讯作者：
Robbins, DC