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Impact of repeated measures and sample selection on genome-wide association studies of fasting glucose.

TitleImpact of repeated measures and sample selection on genome-wide association studies of fasting glucose.
Publication TypeJournal Article
Year of Publication2010
AuthorsRasmussen-Torvik LJ, Alonso A, Li M, Kao W, Köttgen A, Yan Y, Couper DJ, Boerwinkle E, Bielinski SJ
Secondary AuthorsPankow JS
JournalGenet Epidemiol
Volume34
Issue7
Pagination665-73
Date Published2010 Nov
ISSN1098-2272
KeywordsAged, Atherosclerosis, Blood Glucose, Cohort Studies, Diabetes Mellitus, Type 2, Fasting, Female, Genetic Association Studies, Genome-Wide Association Study, Humans, Male, Middle Aged, Molecular Epidemiology, Polymorphism, Single Nucleotide, Prospective Studies
Abstract

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

DOI10.1002/gepi.20525
Alternate JournalGenet Epidemiol
PubMed ID20839289
PubMed Central IDPMC2964401
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
HHSN268200625226C / / PHS HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
T32 HL007779 / HL / NHLBI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
HL07779 / HL / NHLBI NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States