| Common variants at 30 loci contribute to polygenic dyslipidemia. | |
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MedLine Citation:
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PMID: 19060906 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Sekar Kathiresan; Cristen J Willer; Gina M Peloso; Serkalem Demissie; Kiran Musunuru; Eric E Schadt; Lee Kaplan; Derrick Bennett; Yun Li; Toshiko Tanaka; Benjamin F Voight; Lori L Bonnycastle; Anne U Jackson; Gabriel Crawford; Aarti Surti; Candace Guiducci; Noel P Burtt; Sarah Parish; Robert Clarke; Diana Zelenika; Kari A Kubalanza; Mario A Morken; Laura J Scott; Heather M Stringham; Pilar Galan; Amy J Swift; Johanna Kuusisto; Richard N Bergman; Jouko Sundvall; Markku Laakso; Luigi Ferrucci; Paul Scheet; Serena Sanna; Manuela Uda; Qiong Yang; Kathryn L Lunetta; Josée Dupuis; Paul I W de Bakker; Christopher J O'Donnell; John C Chambers; Jaspal S Kooner; Serge Hercberg; Pierre Meneton; Edward G Lakatta; Angelo Scuteri; David Schlessinger; Jaakko Tuomilehto; Francis S Collins; Leif Groop; David Altshuler; Rory Collins; G Mark Lathrop; Olle Melander; Veikko Salomaa; Leena Peltonen; Marju Orho-Melander; Jose M Ordovas; Michael Boehnke; Gonçalo R Abecasis; Karen L Mohlke; L Adrienne Cupples |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2008-12-07 |
Journal Detail:
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Title: Nature genetics Volume: 41 ISSN: 1546-1718 ISO Abbreviation: Nat. Genet. Publication Date: 2009 Jan |
Date Detail:
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Created Date: 2008-12-29 Completed Date: 2009-01-23 Revised Date: 2011-10-11 |
Medline Journal Info:
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Nlm Unique ID: 9216904 Medline TA: Nat Genet Country: United States |
Other Details:
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Languages: eng Pagination: 56-65 Citation Subset: IM |
Affiliation:
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Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Alleles Cholesterol, HDL / blood Cholesterol, LDL / blood Dyslipidemias / blood, genetics* Female Gene Expression Regulation Genome-Wide Association Study Humans Liver / metabolism Male Meta-Analysis as Topic Middle Aged Multifactorial Inheritance / genetics* Phenotype Polymorphism, Single Nucleotide / genetics* Quantitative Trait Loci / genetics* RNA, Messenger / genetics, metabolism Reproducibility of Results Syndrome Triglycerides / blood |
| Grant Support | |
ID/Acronym/Agency:
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089061//Wellcome Trust; 53-K06-5-10//PHS HHS; DK062370/DK/NIDDK NIH HHS; DK072193/DK/NIDDK NIH HHS; HG02651/HG/NHGRI NIH HHS; HL-54776/HL/NHLBI NIH HHS; HL084729/HL/NHLBI NIH HHS; K23 HL083102-03/HL/NHLBI NIH HHS; N01-HC-25195/HC/NHLBI NIH HHS; N01-HG-65403/HG/NHGRI NIH HHS; P30 DK040561-13/DK/NIDDK NIH HHS; R01 DK072193-01/DK/NIDDK NIH HHS; R01 DK072193-02/DK/NIDDK NIH HHS; R01 DK072193-03/DK/NIDDK NIH HHS; R01 DK072193-04/DK/NIDDK NIH HHS; R01 DK075030-02/DK/NIDDK NIH HHS; R01 HL054776-11/HL/NHLBI NIH HHS; //British Heart Foundation; //Cancer Research UK; //Department of Health; //Medical Research Council |
| Chemical | |
Reg. No./Substance:
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0/Cholesterol, HDL; 0/Cholesterol, LDL; 0/RNA, Messenger; 0/Triglycerides |
| Comments/Corrections | |
Comment In:
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Nat Genet. 2009 Jan;41(1):5-6
[PMID:
19112455
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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