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Common variants at 30 loci contribute to polygenic dyslipidemia

Kathiresan, Sekar; Willer, Cristen J.; Peloso, Gina M.; Demissie, Serkalem; Musunuru, Kiran; Schadt, Eric E.; Kaplan, Lee; Bennett, Derrick; Li, Yun and Tanaka, Toshiko, et al. (2009) In Nature Genetics 41(1). p.56-65
Abstract
Blood low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels are risk factors for cardiovascular disease. To dissect the polygenic basis of these traits, we conducted genome-wide association screens in 19,840 individuals and replication in up to 20,623 individuals. We identified 30 distinct loci associated with lipoprotein concentrations (each with P < 5 x 10(-8)), including 11 loci that reached genome-wide significance for the first time. The 11 newly defined loci include common variants associated with LDL cholesterol near ABCG8, MAFB, HNF1A and TIMD4; with HDL cholesterol near ANGPTL4, FADS1-FADS2-FADS3, HNF4A, LCAT, PLTP and TTC39B; and with triglycerides near AMAC1L2,... (More)
Blood low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels are risk factors for cardiovascular disease. To dissect the polygenic basis of these traits, we conducted genome-wide association screens in 19,840 individuals and replication in up to 20,623 individuals. We identified 30 distinct loci associated with lipoprotein concentrations (each with P < 5 x 10(-8)), including 11 loci that reached genome-wide significance for the first time. The 11 newly defined loci include common variants associated with LDL cholesterol near ABCG8, MAFB, HNF1A and TIMD4; with HDL cholesterol near ANGPTL4, FADS1-FADS2-FADS3, HNF4A, LCAT, PLTP and TTC39B; and with triglycerides near AMAC1L2, FADS1-FADS2-FADS3 and PLTP. The proportion of individuals exceeding clinical cut points for high LDL cholesterol, low HDL cholesterol and high triglycerides varied according to an allelic dosage score (P < 10(-15) for each trend). These results suggest that the cumulative effect of multiple common variants contributes to polygenic dyslipidemia. (Less)
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Nature Genetics
volume
41
issue
1
pages
56 - 65
publisher
Nature Publishing Group
external identifiers
  • wos:000262085300016
  • scopus:58149163149
ISSN
1546-1718
DOI
10.1038/ng.291
language
English
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yes
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3bda50e8-bbd1-4784-a049-cf6d1364419b (old id 1313138)
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2009-03-12 12:07:50
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@article{3bda50e8-bbd1-4784-a049-cf6d1364419b,
  abstract     = {Blood low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels are risk factors for cardiovascular disease. To dissect the polygenic basis of these traits, we conducted genome-wide association screens in 19,840 individuals and replication in up to 20,623 individuals. We identified 30 distinct loci associated with lipoprotein concentrations (each with P &lt; 5 x 10(-8)), including 11 loci that reached genome-wide significance for the first time. The 11 newly defined loci include common variants associated with LDL cholesterol near ABCG8, MAFB, HNF1A and TIMD4; with HDL cholesterol near ANGPTL4, FADS1-FADS2-FADS3, HNF4A, LCAT, PLTP and TTC39B; and with triglycerides near AMAC1L2, FADS1-FADS2-FADS3 and PLTP. The proportion of individuals exceeding clinical cut points for high LDL cholesterol, low HDL cholesterol and high triglycerides varied according to an allelic dosage score (P &lt; 10(-15) for each trend). These results suggest that the cumulative effect of multiple common variants contributes to polygenic dyslipidemia.},
  author       = {Kathiresan, Sekar and Willer, Cristen J. and Peloso, Gina M. and Demissie, Serkalem and Musunuru, Kiran and Schadt, Eric E. and Kaplan, Lee and Bennett, Derrick and Li, Yun and Tanaka, Toshiko and Voight, Benjamin F. and Bonnycastle, Lori L. and Jackson, Anne U. and Crawford, Gabriel and Surti, Aarti and Guiducci, Candace and Burtt, Noel P. and Parish, Sarah and Clarke, Robert and Zelenika, Diana and Kubalanza, Kari A. and Morken, Mario A. and Scott, Laura J. and Stringham, Heather M. and Galan, Pilar and Swift, Amy J. and Kuusisto, Johanna and Bergman, Richard N. and Sundvall, Jouko and Laakso, Markku and Ferrucci, Luigi and Scheet, Paul and Sanna, Serena and Uda, Manuela and Yang, Qiong and Lunetta, Kathryn L. and Dupuis, Josee and de Bakker, Paul I. W. and O'Donnell, Christopher J. and Chambers, John C. and Kooner, Jaspal S. and Hercberg, Serge and Meneton, Pierre and Lakatta, Edward G. and Scuteri, Angelo and Schlessinger, David and Tuomilehto, Jaakko and Collins, Francis S. and Groop, Leif and Altshuler, David and Collins, Rory and Lathrop, G. Mark and Melander, Olle and Salomaa, Veikko and Peltonen, Leena and Orho-Melander, Marju and Ordovas, Jose M. and Boehnke, Michael and Abecasis, Goncalo R. and Mohlke, Karen L. and Cupples, L. Adrienne},
  issn         = {1546-1718},
  language     = {eng},
  number       = {1},
  pages        = {56--65},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {Common variants at 30 loci contribute to polygenic dyslipidemia},
  url          = {http://dx.doi.org/10.1038/ng.291},
  volume       = {41},
  year         = {2009},
}