TY - JOUR T1 - Biological, clinical and population relevance of 95 loci for blood lipids. JF - Nature Y1 - 2010 A1 - Teslovich, Tanya M A1 - Musunuru, Kiran A1 - Smith, Albert V A1 - Edmondson, Andrew C A1 - Stylianou, Ioannis M A1 - Koseki, Masahiro A1 - Pirruccello, James P A1 - Ripatti, Samuli A1 - Chasman, Daniel I A1 - Willer, Cristen J A1 - Johansen, Christopher T A1 - Fouchier, Sigrid W A1 - Isaacs, Aaron A1 - Peloso, Gina M A1 - Barbalic, Maja A1 - Ricketts, Sally L A1 - Bis, Joshua C A1 - Aulchenko, Yurii S A1 - Thorleifsson, Gudmar A1 - Feitosa, Mary F A1 - Chambers, John A1 - Orho-Melander, Marju A1 - Melander, Olle A1 - Johnson, Toby A1 - Li, Xiaohui A1 - Guo, Xiuqing A1 - Li, Mingyao A1 - Shin Cho, Yoon A1 - Jin Go, Min A1 - Jin Kim, Young A1 - Lee, Jong-Young A1 - Park, Taesung A1 - Kim, Kyunga A1 - Sim, Xueling A1 - Twee-Hee Ong, Rick A1 - Croteau-Chonka, Damien C A1 - Lange, Leslie A A1 - Smith, Joshua D A1 - Song, Kijoung A1 - Hua Zhao, Jing A1 - Yuan, Xin A1 - Luan, Jian'an A1 - Lamina, Claudia A1 - Ziegler, Andreas A1 - Zhang, Weihua A1 - Zee, Robert Y L A1 - Wright, Alan F A1 - Witteman, Jacqueline C M A1 - Wilson, James F A1 - Willemsen, Gonneke A1 - Wichmann, H-Erich A1 - Whitfield, John B A1 - Waterworth, Dawn M A1 - Wareham, Nicholas J A1 - Waeber, Gérard A1 - Vollenweider, Peter A1 - Voight, Benjamin F A1 - Vitart, Veronique A1 - Uitterlinden, André G A1 - Uda, Manuela A1 - Tuomilehto, Jaakko A1 - Thompson, John R A1 - Tanaka, Toshiko A1 - Surakka, Ida A1 - Stringham, Heather M A1 - Spector, Tim D A1 - Soranzo, Nicole A1 - Smit, Johannes H A1 - Sinisalo, Juha A1 - Silander, Kaisa A1 - Sijbrands, Eric J G A1 - Scuteri, Angelo A1 - Scott, James A1 - Schlessinger, David A1 - Sanna, Serena A1 - Salomaa, Veikko A1 - Saharinen, Juha A1 - Sabatti, Chiara A1 - Ruokonen, Aimo A1 - Rudan, Igor A1 - Rose, Lynda M A1 - Roberts, Robert A1 - Rieder, Mark A1 - Psaty, Bruce M A1 - Pramstaller, Peter P A1 - Pichler, Irene A1 - Perola, Markus A1 - Penninx, Brenda W J H A1 - Pedersen, Nancy L A1 - Pattaro, Cristian A1 - Parker, Alex N A1 - Paré, Guillaume A1 - Oostra, Ben A A1 - O'Donnell, Christopher J A1 - Nieminen, Markku S A1 - Nickerson, Deborah A A1 - Montgomery, Grant W A1 - Meitinger, Thomas A1 - McPherson, Ruth A1 - McCarthy, Mark I A1 - McArdle, Wendy A1 - Masson, David A1 - Martin, Nicholas G A1 - Marroni, Fabio A1 - Mangino, Massimo A1 - Magnusson, Patrik K E A1 - Lucas, Gavin A1 - Luben, Robert A1 - Loos, Ruth J F A1 - Lokki, Marja-Liisa A1 - Lettre, Guillaume A1 - Langenberg, Claudia A1 - Launer, Lenore J A1 - Lakatta, Edward G A1 - Laaksonen, Reijo A1 - Kyvik, Kirsten O A1 - Kronenberg, Florian A1 - König, Inke R A1 - Khaw, Kay-Tee A1 - Kaprio, Jaakko A1 - Kaplan, Lee M A1 - Johansson, Asa A1 - Jarvelin, Marjo-Riitta A1 - Janssens, A Cecile J W A1 - Ingelsson, Erik A1 - Igl, Wilmar A1 - Kees Hovingh, G A1 - Hottenga, Jouke-Jan A1 - Hofman, Albert A1 - Hicks, Andrew A A1 - Hengstenberg, Christian A1 - Heid, Iris M A1 - Hayward, Caroline A1 - Havulinna, Aki S A1 - Hastie, Nicholas D A1 - Harris, Tamara B A1 - Haritunians, Talin A1 - Hall, Alistair S A1 - Gyllensten, Ulf A1 - Guiducci, Candace A1 - Groop, Leif C A1 - Gonzalez, Elena A1 - Gieger, Christian A1 - Freimer, Nelson B A1 - Ferrucci, Luigi A1 - Erdmann, Jeanette A1 - Elliott, Paul A1 - Ejebe, Kenechi G A1 - Döring, Angela A1 - Dominiczak, Anna F A1 - Demissie, Serkalem A1 - Deloukas, Panagiotis A1 - de Geus, Eco J C A1 - de Faire, Ulf A1 - Crawford, Gabriel A1 - Collins, Francis S A1 - Chen, Yii-der I A1 - Caulfield, Mark J A1 - Campbell, Harry A1 - Burtt, Noel P A1 - Bonnycastle, Lori L A1 - Boomsma, Dorret I A1 - Boekholdt, S Matthijs A1 - Bergman, Richard N A1 - Barroso, Inês A1 - Bandinelli, Stefania A1 - Ballantyne, Christie M A1 - Assimes, Themistocles L A1 - Quertermous, Thomas A1 - Altshuler, David A1 - Seielstad, Mark A1 - Wong, Tien Y A1 - Tai, E-Shyong A1 - Feranil, Alan B A1 - Kuzawa, Christopher W A1 - Adair, Linda S A1 - Taylor, Herman A A1 - Borecki, Ingrid B A1 - Gabriel, Stacey B A1 - Wilson, James G A1 - Holm, Hilma A1 - Thorsteinsdottir, Unnur A1 - Gudnason, Vilmundur A1 - Krauss, Ronald M A1 - Mohlke, Karen L A1 - Ordovas, Jose M A1 - Munroe, Patricia B A1 - Kooner, Jaspal S A1 - Tall, Alan R A1 - Hegele, Robert A A1 - Kastelein, John J P A1 - Schadt, Eric E A1 - Rotter, Jerome I A1 - Boerwinkle, Eric A1 - Strachan, David P A1 - Mooser, Vincent A1 - Stefansson, Kari A1 - Reilly, Muredach P A1 - Samani, Nilesh J A1 - Schunkert, Heribert A1 - Cupples, L Adrienne A1 - Sandhu, Manjinder S A1 - Ridker, Paul M A1 - Rader, Daniel J A1 - van Duijn, Cornelia M A1 - Peltonen, Leena A1 - Abecasis, Goncalo R A1 - Boehnke, Michael A1 - Kathiresan, Sekar KW - African Americans KW - Animals KW - Asian Continental Ancestry Group KW - Cholesterol, HDL KW - Cholesterol, LDL KW - Coronary Artery Disease KW - Europe KW - European Continental Ancestry Group KW - Female KW - Genetic Loci KW - Genome-Wide Association Study KW - Genotype KW - Humans KW - Lipid Metabolism KW - Lipids KW - Liver KW - Male KW - Mice KW - N-Acetylgalactosaminyltransferases KW - Phenotype KW - Polymorphism, Single Nucleotide KW - Protein Phosphatase 1 KW - Reproducibility of Results KW - Triglycerides AB -

Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.

VL - 466 IS - 7307 U1 - http://www.ncbi.nlm.nih.gov/pubmed/20686565?dopt=Abstract ER -