Genetic variants influencing circulating lipid levels and risk of coronary artery disease.

Détails

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Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_E62B304DA11E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Genetic variants influencing circulating lipid levels and risk of coronary artery disease.
Périodique
Arteriosclerosis, Thrombosis, and Vascular Biology
Auteur(s)
Waterworth D.M., Ricketts S.L., Song K., Chen L., Zhao J.H., Ripatti S., Aulchenko Y.S., Zhang W., Yuan X., Lim N., Luan J., Ashford S., Wheeler E., Young E.H., Hadley D., Thompson J.R., Braund P.S., Johnson T., Struchalin M., Surakka I., Luben R., Khaw K.T., Rodwell S.A., Loos R.J., Boekholdt S.M., Inouye M., Deloukas P., Elliott P., Schlessinger D., Sanna S., Scuteri A., Jackson A., Mohlke K.L., Tuomilehto J., Roberts R., Stewart A., Kesäniemi Y.A., Mahley R.W., Grundy S.M., McArdle W., McArdle W., Cardon L., Waeber G., Vollenweider P., Chambers J.C., Boehnke M., Abecasis G.R., Salomaa V., Järvelin M.R., Ruokonen A., Barroso I., Epstein S.E., Hakonarson H.H., Rader D.J., Reilly M.P., Witteman J.C., Hall A.S., Samani N.J., Strachan D.P., Barter P., van Duijn C.M., Kooner J.S., Peltonen L., Wareham N.J., McPherson R., Mooser V., Sandhu M.S.
Collaborateur(s)
Wellcome Trust Case Control Consortium
ISSN
1524-4636 (Electronic)
ISSN-L
1079-5642
Statut éditorial
Publié
Date de publication
2010
Peer-reviewed
Oui
Volume
30
Numéro
11
Pages
2264-2276
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Résumé
OBJECTIVE: 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. METHODS AND RESULTS: 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)). CONCLUSIONS: 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.
Mots-clé
Asian Continental Ancestry Group, Cholesterol, HDL/blood, Cholesterol, HDL/genetics, Cholesterol, LDL/blood, Cholesterol, LDL/genetics, Coronary Artery Disease/genetics, European Continental Ancestry Group, Genetic Variation, Genome-Wide Association Study, Humans, Lipid Metabolism/genetics, Polymorphism, Single Nucleotide, Risk Factors, Triglycerides/blood, Triglycerides/genetics, Colaus Study
Pubmed
Web of science
Open Access
Oui
Création de la notice
01/12/2010 11:20
Dernière modification de la notice
20/08/2019 16:09
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