Biological, clinical and population relevance of 95 loci for blood lipids.

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

Nature 2010 Aug;466(7307):707-13

Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA.

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.

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http://dx.doi.org/10.1038/nature09270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039276PMC
August 2010
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