Citation
Teslovich, Tanya M.; Musunuru, Kiran; Smith, Albert V.; Edmondson, Andrew C.; Stylianou, Ioannis M.; Koseki, Masahiro; Pirruccello, James P.; Ripatti, Samuli; Chasman, Daniel I.; & Willer, Cristen J., et al. (2010). Biological, Clinical and Population Relevance of 95 Loci for Blood Lipids. Nature, 466(7307), 707-713. PMCID: PMC3039276Abstract
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.URL
http://dx.doi.org/10.1038/nature09270Reference Type
Journal ArticleYear Published
2010Journal Title
NatureAuthor(s)
Teslovich, Tanya M.Musunuru, Kiran
Smith, Albert V.
Edmondson, Andrew C.
Stylianou, Ioannis M.
Koseki, Masahiro
Pirruccello, James P.
Ripatti, Samuli
Chasman, Daniel I.
Willer, Cristen J.
Johansen, Christopher T.
Fouchier, Sigrid W.
Isaacs, Aaron J.
Peloso, Gina M.
Barbalic, Maja
Ricketts, Sally L.
Bis, Joshua C.
Aulchenko, Yurii S.
Thorleifsson, Gudmar
Feitosa, Mary F.
Chambers, John C.
Orho-Melander, Marju
Melander, Olle
Johnson, Toby
Li, Xiaohui
Guo, Xiuqing
Li, Mingyao
Cho, Yoon Shin
Go, Min Jin
Kim, Young Jin
Lee, Jong-Young
Park, Taesung
Kim, Kyunga
Sim, Xueling
Ong, Rick Twee-Hee
Croteau-Chonka, Damien C.
Lange, Leslie A.
Smith, Joshua D.
Song, Kijoung
Zhao, Jing Hua
Yuan, Xin
Luan, Jian'an
Lamina, Claudia
Ziegler, Andreas
Zhang, Weihua
Zee, Robert Y. L.
Wright, Alan F.
Witteman, Jacqueline C. M.
Wilson, James F.
Willemsen, Gonneke
Wichmann, H. Erich
Whitfield, John B.
Waterworth, Dawn M.
Wareham, Nicholas J.
Waeber, Gérard
Vollenweider, Peter
Voight, Benjamin F.
Vitart, Veronique
Uitterlinden, Andre G.
Uda, Manuela
Tuomilehto, Jaakko
Thompson, John R.
Tanaka, Toshiko
Surakka, Ida
Stringham, Heather M.
Spector, Timothy D.
Soranzo, Nicole
Smit, Johannes H.
Sinisalo, Juha
Silander, Kaisa
Sijbrands, Eric
Scuteri, Angelo
Scott, James
Schlessinger, David
Sanna, Serena
Salomaa, Veikko
Saharinen, Juha
Sabatti, Chiara
Ruokonen, Aimo
Rudan, Igor
Rose, Lynda M.
Roberts, Robert
Rieder, Mark
Psaty, Bruce M.
Pramstaller, Peter P.
Pichler, Irene
Perola, Markus
Penninx, Brenda W. J. H. W.
Pedersen, Nancy L.
Pattaro, Cristian
Parker, Alex N.
Pare, Guillaume
Oostra, Ben A.
O'Donnell, Christopher J.
Nieminen, Markku S.
Nickerson, Deborah A.
Montgomery, Grant W.
Meitinger, Thomas
McPherson, Ruth
McCarthy, Mark I.
McArdle, Wendy L.
Masson, David
Martin, Nicholas G.
Marroni, Fabio
Mangino, Massimo
Magnusson, Patrik K. E.
Lucas, Gavin
Luben, Robert
Loos, Ruth J. F.
Lokki, Marja-Liisa
Lettre, Guillaume
Langenberg, Claudia
Launer, Lenore J.
Lakatta, Edward G.
Laaksonen, Reijo
Kyvik, Kirsten O.
Kronenberg, Florian
König, Inke R.
Khaw, Kay-Tee
Kaprio, Jaakko
Kaplan, Lee M.
Johansson, Åsa
Jarvelin, Marjo-Riitta
Janssens, A. Cecile J. W.
Ingelsson, Erik
Igl, Wilmar
Hovingh, G. Kees
Hottenga, Jouke-Jan
Hofman, Albert
Hicks, Andrew A.
Hengstenberg, Christian
Heid, Iris M.
Hayward, Caroline
Havulinna, Aki S.
Hastie, Nicholas D.
Harris, Tamara B.
Haritunians, Talin
Hall, Alistair S.
Gyllensten, Ulf
Guiducci, Candace
Groop, Leif C.
Gonzalez, Elena
Gieger, Christian
Freimer, Nelson B.
Ferrucci, Luigi
Erdmann, Jeanette
Elliott, Paul
Ejebe, Kenechi G.
Döring, Angela
Dominiczak, Anna F.
Demissie, Serkalem
Deloukas, Panagiotis
de Geus, Eco J. C.
de Faire, Ulf
Crawford, Gabriel
Collins, Francis S.
Chen, Yii-Der Ida
Caulfield, Mark J.
Campbell, Harry
Burtt, Noel P.
Bonnycastle, Lori L.
Boomsma, Dorret I.
Boekholdt, S. Matthijs
Bergman, Richard N.
Barroso, Inês
Bandinelli, Stefania
Ballantyne, Christie M.
Assimes, Themistocles L.
Quertermous, Thomas
Altshuler, David
Seielstad, Mark
Wong, Tien Yin
Tai, E. Shyong
Feranil, Alan B.
Kuzawa, Christopher W.
Adair, Linda S.
Taylor, Herman A., Jr.
Borecki, Ingrid B.
Gabriel, Stacey B.
Wilson, James G.
Holm, Hilma
Thorsteinsdottir, Unnur
Gudnason, Vilmundur G.
Krauss, Ronald M.
Mohlke, Karen L.
Ordóñez, José M.
Munroe, Patricia B.
Kooner, Jaspal Singh S.
Tall, Alan R.
Hegele, Robert A.
Kastelein, John J. P.
Schadt, Eric E.
Rotter, Jerome I.
Boerwinkle, Eric A.
Strachan, David P.
Mooser, Vincent E.
Stefansson, Kari
Reilly, Muredach P.
Samani, Nilesh J.
Schunkert, Heribert
Cupples, L. Adrienne
Sandhu, Manjinder S.
Ridker, Paul M.
Rader, Daniel J.
van Duijn, Cornelia M.
Peltonen, Leena
Abecasis, Gonçalo R.
Boehnke, Michael
Kathiresan, Sekar