Genetic Variants Influencing Circulating Lipid Levels and Risk of Coronary Artery Disease Academic Article uri icon

abstract

  • Genetic 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.We 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)).We 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.

authors

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

publication date

  • November 2010