• Dawn M Waterworth, Sally L Ricketts, Kijoung Song, Li Chen, Jing Hua Zhao, Samuli Ripatti, Yurii S Aulchenko, Weihua Zhang, Xin Yuan, Noha Lim, Jian'an Luan, Sofie Ashford, Eleanor Wheeler, Elizabeth H Young, David Hadley, John R Thompson, Peter S Braund, Toby Johnson, Maksim Struchalin, Ida Surakka, Robert Luben, Kay-Tee Khaw, Sheila A Rodwell, Ruth J F Loos, S Matthijs Boekholdt, Michael Inouye, Panagiotis Deloukas, Paul Elliott, David Schlessinger, Serena Sanna, Angelo Scuteri, Anne Jackson, Karen L Mohlke, Jaako Tuomilehto, Robert Roberts, Alexandre Stewart, Y Antero Kesäniemi, Robert W Mahley, Scott M Grundy, Wellcome Trust Case Control Consortium, Wendy McArdle, Lon Cardon, Gérard Waeber, Peter Vollenweider, John C Chambers, Michael Boehnke, Gonçalo R Abecasis, Veikko Salomaa, Marjo-Riitta Järvelin, Aimo Ruokonen, Inês Barroso, Stephen E Epstein, Hakon H Hakonarson, Daniel J Rader, Muredach P Reilly, Jacqueline C M Witteman, Alistair S Hall, Nilesh J Samani, David P Strachan, Philip Barter, Cornelia M van Duijn, Jaspal S Kooner, Leena Peltonen, Nicholas J Wareham, Ruth McPherson, Vincent Mooser, and Manjinder S Sandhu.
• Genetics Division, GlaxoSmithKline R&D, King of Prussia, PA, USA.
• Arterioscler. Thromb. Vasc. Biol. 2010 Nov 1; 30 (11): 2264-76.

ObjectiveGenetic studies might provide new insights into the biological mechanisms underlying lipid metabolism and risk of CAD. We therefore conducted a genome-wide association study to identify novel genetic determinants of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides.Methods And ResultsWe combined genome-wide association data from 8 studies, comprising up to 17 723 participants with information on circulating lipid concentrations. We did independent replication studies in up to 37 774 participants from 8 populations and also in a population of Indian Asian descent. We also assessed the association between single-nucleotide polymorphisms (SNPs) at lipid loci and risk of CAD in up to 9 633 cases and 38 684 controls. We identified 4 novel genetic loci that showed reproducible associations with lipids (probability values, 1.6×10(-8) to 3.1×10(-10)). These include a potentially functional SNP in the SLC39A8 gene for HDL-C, an SNP near the MYLIP/GMPR and PPP1R3B genes for LDL-C, and at the AFF1 gene for triglycerides. SNPs showing strong statistical association with 1 or more lipid traits at the CELSR2, APOB, APOE-C1-C4-C2 cluster, LPL, ZNF259-APOA5-A4-C3-A1 cluster and TRIB1 loci were also associated with CAD risk (probability values, 1.1×10(-3) to 1.2×10(-9)).ConclusionsWe have identified 4 novel loci associated with circulating lipids. We also show that in addition to those that are largely associated with LDL-C, genetic loci mainly associated with circulating triglycerides and HDL-C are also associated with risk of CAD. These findings potentially provide new insights into the biological mechanisms underlying lipid metabolism and CAD risk.

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