Discovery and refinement of loci associated with lipid levels.
Discovery and refinement of loci associated with lipid levels.
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DOI：
10.1038/ng.2797
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发表时间：
2013-11
期刊：
影响因子：
30.8
通讯作者：
Abecasis, Goncalo R
中科院分区：
文献类型：
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作者：
Willer, Cristen J;Schmidt, Ellen M;Sengupta, Sebanti;Peloso, Gina M;Gustafsson, Stefan;Kanoni, Stavroula;Ganna, Andrea;Chen, Jin;Buchkovich, Martin L;Mora, Samia;Beckmann, Jacques S;Bragg-Gresham, Jennifer L;Chang, Hsing-Yi;Demirkan, Ayse;Den Hertog, Heleen M;Do, Ron;Donnelly, Louise A;Ehret, Georg B;Esko, Tonu;Feitosa, Mary F;Ferreira, Teresa;Fischer, Krista;Fontanillas, Pierre;Fraser, Ross M;Freitag, Daniel F;Gurdasani, Deepti;Heikkila, Kauko;Hypponen, Elina;Isaacs, Aaron;Jackson, Anne U;Johansson, Asa;Johnson, Toby;Kaakinen, Marika;Kettunen, Johannes;Kleber, Marcus E;Li, Xiaohui;Luan, Jian'an;Lyytikainen, Leo-Pekka;Magnusson, Patrik K E;Mangino, Massimo;Mihailov, Evelin;Montasser, May E;Muller-Nurasyid, Martina;Nolte, Ilja M;O'Connell, Jeffrey R;Palmer, Cameron D;Perola, Markus;Petersen, Ann-Kristin;Sanna, Serena;Saxena, Richa;Service, Susan K;Shah, Sonia;Shungin, Dmitry;Sidore, Carlo;Song, Ci;Strawbridge, Rona J;Surakka, Ida;Tanaka, Toshiko;Teslovich, Tanya M;Thorleifsson, Gudmar;Van den Herik, Evita G;Voight, Benjamin F;Volcik, Kelly A;Waite, Lindsay L;Wong, Andrew;Wu, Ying;Zhang, Weihua;Absher, Devin;Asiki, Gershim;Barroso, Ines;Been, Latonya F;Bolton, Jennifer L;Bonnycastle, Lori L;Brambilla, Paolo;Burnett, Mary S;Cesana, Giancarlo;Dimitriou, Maria;Doney, Alex S F;Doring, Angela;Elliott, Paul;Epstein, Stephen E;Ingi Eyjolfsson, Gudmundur;Gigante, Bruna;Goodarzi, Mark O;Grallert, Harald;Gravito, Martha L;Groves, Christopher J;Hallmans, Goran;Hartikainen, Anna-Liisa;Hayward, Caroline;Hernandez, Dena;Hicks, Andrew A;Holm, Hilma;Hung, Yi-Jen;Illig, Thomas;Jones, Michelle R;Kaleebu, Pontiano;Kastelein, John J P;Khaw, Kay-Tee;Kim, Eric;Klopp, Norman;Komulainen, Pirjo;Kumari, Meena;Langenberg, Claudia;Lehtimaki, Terho;Lin, Shih-Yi;Lindstrom, Jaana;Loos, Ruth J F;Mach, Francois;McArdle, Wendy L;Meisinger, Christa;Mitchell, Braxton D;Muller, Gabrielle;Nagaraja, Ramaiah;Narisu, Narisu;Nieminen, Tuomo V M;Nsubuga, Rebecca N;Olafsson, Isleifur;Ong, Ken K;Palotie, Aarno;Papamarkou, Theodore;Pomilla, Cristina;Pouta, Anneli;Rader, Daniel J;Reilly, Muredach P;Ridker, Paul M;Rivadeneira, Fernando;Rudan, Igor;Ruokonen, Aimo;Samani, Nilesh;Scharnagl, Hubert;Seeley, Janet;Silander, Kaisa;Stancakova, Alena;Stirrups, Kathleen;Swift, Amy J;Tiret, Laurence;Uitterlinden, Andre G;van Pelt, L Joost;Vedantam, Sailaja;Wainwright, Nicholas;Wijmenga, Cisca;Wild, Sarah H;Willemsen, Gonneke;Wilsgaard, Tom;Wilson, James F;Young, Elizabeth H;Zhao, Jing Hua;Adair, Linda S;Arveiler, Dominique;Assimes, Themistocles L;Bandinelli, Stefania;Bennett, Franklyn;Bochud, Murielle;Boehm, Bernhard O;Boomsma, Dorret I;Borecki, Ingrid B;Bornstein, Stefan R;Bovet, Pascal;Burnier, Michel;Campbell, Harry;Chakravarti, Aravinda;Chambers, John C;Chen, Yii-Der Ida;Collins, Francis S;Cooper, Richard S;Danesh, John;Dedoussis, George;de Faire, Ulf;Feranil, Alan B;Ferrieres, Jean;Ferrucci, Luigi;Freimer, Nelson B;Gieger, Christian;Groop, Leif C;Gudnason, Vilmundur;Gyllensten, Ulf;Hamsten, Anders;Harris, Tamara B;Hingorani, Aroon;Hirschhorn, Joel N;Hofman, Albert;Hovingh, G Kees;Hsiung, Chao Agnes;Humphries, Steve E;Hunt, Steven C;Hveem, Kristian;Iribarren, Carlos;Jarvelin, Marjo-Riitta;Jula, Antti;Kahonen, Mika;Kaprio, Jaakko;Kesaniemi, Antero;Kivimaki, Mika;Kooner, Jaspal S;Koudstaal, Peter J;Krauss, Ronald M;Kuh, Diana;Kuusisto, Johanna;Kyvik, Kirsten O;Laakso, Markku;Lakka, Timo A;Lind, Lars;Lindgren, Cecilia M;Martin, Nicholas G;Marz, Winfried;McCarthy, Mark I;McKenzie, Colin A;Meneton, Pierre;Metspalu, Andres;Moilanen, Leena;Morris, Andrew D;Munroe, Patricia B;Njolstad, Inger;Pedersen, Nancy L;Power, Chris;Pramstaller, Peter P;Price, Jackie F;Psaty, Bruce M;Quertermous, Thomas;Rauramaa, Rainer;Saleheen, Danish;Salomaa, Veikko;Sanghera, Dharambir K;Saramies, Jouko;Schwarz, Peter E H;Sheu, Wayne H-H;Shuldiner, Alan R;Siegbahn, Agneta;Spector, Tim D;Stefansson, Kari;Strachan, David P;Tayo, Bamidele O;Tremoli, Elena;Tuomilehto, Jaakko;Uusitupa, Matti;van Duijn, Cornelia M;Vollenweider, Peter;Wallentin, Lars;Wareham, Nicholas J;Whitfield, John B;Wolffenbuttel, Bruce H R;Ordovas, Jose M;Boerwinkle, Eric;Palmer, Colin N A;Thorsteinsdottir, Unnur;Chasman, Daniel I;Rotter, Jerome I;Franks, Paul W;Ripatti, Samuli;Cupples, L Adrienne;Sandhu, Manjinder S;Rich, Stephen S;Boehnke, Michael;Deloukas, Panos;Kathiresan, Sekar;Mohlke, Karen L;Ingelsson, Erik;Abecasis, Goncalo R
低密度脂蛋白（LDL）胆固醇、高密度脂蛋白（HDL）胆固醇、甘油三酯和总胆固醇是冠状动脉疾病的可遗传、可改变的危险因素。为了确定新的基因座和改进影响这些脂质的已知基因座，我们使用全基因组和定制基因分型阵列检查了188，578名个体。我们确定并注释了157个与P < 5×10−8的血脂水平相关的基因座，包括62个以前与人类血脂水平无关的基因座。在欧洲，东亚，南亚和非洲血统的个体中使用密集基因分型，我们缩小了12个位点的关联信号。我们发现与血脂相关的基因座通常与心血管和代谢特征相关，包括冠状动脉疾病，2型糖尿病，血压，腰臀比和体重指数。我们的研究结果说明了来自不同祖先个体的遗传数据的价值，并为调节血脂的生物学机制提供了见解，以指导未来的遗传，生物学和治疗研究。
Low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, and total cholesterol are heritable, modifiable, risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,578 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5×10−8, including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian, and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipids are often associated with cardiovascular and metabolic traits including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio, and body mass index. Our results illustrate the value of genetic data from individuals of diverse ancestries and provide insights into biological mechanisms regulating blood lipids to guide future genetic, biological, and therapeutic research.