| Impact of repeated measures and sample selection on genome-wide association studies of fasting glucose. | |
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MedLine Citation:
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PMID: 20839289 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Although genome-wide association studies (GWAS) have been performed in longitudinal studies, most used only a single trait measure. GWAS of fasting glucose have generally included only normoglycemic individuals. We examined the impact of both repeated measures and sample selection on GWAS in Atherosclerosis Risk In Communities (ARIC), a study which obtained four longitudinal measures of fasting glucose and included both individuals with and without prevalent diabetes. The sample included Caucasians and the Affymetrix 6.0 chip was used for genotyping. Sample sizes for GWAS analyses ranged from 8,372 (first study visit) to 5,782 (average fasting glucose). Candidate SNP analyses with SNPs identified through fasting glucose or diabetes GWAS were conducted in 9,133 individuals, including 761 with prevalent diabetes. For a constant sample size, smaller P-values were obtained for the average measure of fasting glucose compared to values at any single visit, and two additional significant GWAS signals were detected. For four candidate SNPs (rs780094, rs10830963, rs7903146, and rs4607517), the strength of association between genotype and glucose was significantly (P-interaction<0.05) different in those with and without prevalent diabetes, and for all five fasting glucose candidate SNPs (rs780094, rs10830963, rs560887, rs4607517, and rs13266634) the association with measured fasting glucose was more significant in the smaller sample without prevalent diabetes than in the larger combined sample of those with and without diabetes. This analysis demonstrates the potential utility of averaging trait values in GWAS studies and explores the advantage of using only individuals without prevalent diabetes in GWAS of fasting glucose. |
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Authors:
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Laura J Rasmussen-Torvik; Alvaro Alonso; Man Li; Wen Kao; Anna Köttgen; Yu Yan; David Couper; Eric Boerwinkle; Suzette J Bielinski; James S Pankow |
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Publication Detail:
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Type: Journal Article; Multicenter Study; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Genetic epidemiology Volume: 34 ISSN: 1098-2272 ISO Abbreviation: Genet. Epidemiol. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-26 Completed Date: 2011-02-03 Revised Date: 2011-11-01 |
Medline Journal Info:
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Nlm Unique ID: 8411723 Medline TA: Genet Epidemiol Country: United States |
Other Details:
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Languages: eng Pagination: 665-73 Citation Subset: IM |
Copyright Information:
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© 2010 Wiley-Liss, Inc. |
Affiliation:
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Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. ljrtorvik@northwestern.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aged Atherosclerosis / genetics Blood Glucose / genetics* Cohort Studies Diabetes Mellitus, Type 2 / blood, genetics Fasting / blood Female Genetic Association Studies Genome-Wide Association Study / methods*, statistics & numerical data Humans Male Middle Aged Molecular Epidemiology Polymorphism, Single Nucleotide Prospective Studies |
| Grant Support | |
ID/Acronym/Agency:
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HHSN268200625226C//PHS HHS; HL07779/HL/NHLBI NIH HHS; N01-HC-55015/HC/NHLBI NIH HHS; N01-HC-55016/HC/NHLBI NIH HHS; N01-HC-55018/HC/NHLBI NIH HHS; N01-HC-55019/HC/NHLBI NIH HHS; N01-HC-55020/HC/NHLBI NIH HHS; N01-HC-55021/HC/NHLBI NIH HHS; N01-HC-55022/HC/NHLBI NIH HHS; R01HL086694/HL/NHLBI NIH HHS; R01HL087641/HL/NHLBI NIH HHS; R01HL59367/HL/NHLBI NIH HHS; U01HG004402/HG/NHGRI NIH HHS; UL1RR025005/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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