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Transferability and fine-mapping of glucose and insulin quantitative trait loci across populations: CARe, the Candidate Gene Association Resource.

TitleTransferability and fine-mapping of glucose and insulin quantitative trait loci across populations: CARe, the Candidate Gene Association Resource.
Publication TypeJournal Article
Year of Publication2012
AuthorsLiu C-T, C Y Ng M, Rybin D, Adeyemo A, Bielinski SJ, Boerwinkle E, Borecki I, Cade B, Chen YDI, Djousse L, Fornage M, Goodarzi MO, Grant SFA, Guo X, Harris T, Kabagambe E, Kizer JR, Liu Y, Lunetta KL, Mukamal K, Nettleton JA, Pankow JS, Patel SR, Ramos E, Rasmussen-Torvik L, Rich SS, Rotimi CN, Sarpong D, Shriner D, Sims M, Zmuda JM, Redline S, Kao WH, Siscovick D, Florez JC, Rotter JI, Dupuis J, Wilson JG, Bowden DW
Secondary AuthorsMeigs JB
JournalDiabetologia
Volume55
Issue11
Pagination2970-84
Date Published2012 Nov
ISSN1432-0428
KeywordsAdult, African Americans, Aged, Aged, 80 and over, Blood Glucose, Databases, Genetic, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Female, Gene Frequency, Genetic Predisposition to Disease, Humans, Hyperglycemia, Insulin, Linkage Disequilibrium, Male, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Risk Factors, Young Adult
Abstract

AIMS/HYPOTHESIS: Hyperglycaemia disproportionately affects African-Americans (AfAs). We tested the transferability of 18 single-nucleotide polymorphisms (SNPs) associated with glycaemic traits identified in European ancestry (EuA) populations in 5,984 non-diabetic AfAs.

METHODS: We meta-analysed SNP associations with fasting glucose (FG) or insulin (FI) in AfAs from five cohorts in the Candidate Gene Association Resource. We: (1) calculated allele frequency differences, variations in linkage disequilibrium (LD), fixation indices (F(st)s) and integrated haplotype scores (iHSs); (2) tested EuA SNPs in AfAs; and (3) interrogated within ┬▒ 250 kb around each EuA SNP in AfAs.

RESULTS: Allele frequency differences ranged from 0.6% to 54%. F(st) exceeded 0.15 at 6/16 loci, indicating modest population differentiation. All iHSs were

CONCLUSIONS/INTERPRETATION: Few glycaemic SNPs showed strict evidence of transferability from EuA to AfAs. Four loci were significantly associated in both AfAs and those with EuA after accounting for varying LD across ancestral groups, with new signals emerging to aid fine-mapping.

DOI10.1007/s00125-012-2656-4
Alternate JournalDiabetologia
PubMed ID22893027
PubMed Central IDPMC3804308
Grant ListR01 DK078616 / DK / NIDDK NIH HHS / United States
5UC2HL103010-02 / HL / NHLBI NIH HHS / United States
N01-HC-45205 / HC / NHLBI NIH HHS / United States
N01-HC-05187 / HC / NHLBI NIH HHS / United States
UL1 TR000150 / TR / NCATS NIH HHS / United States
R01DK066358 / DK / NIDDK NIH HHS / United States
N01-HC-48047 / HC / NHLBI NIH HHS / United States
M01RR00080 / RR / NCRR NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
RR-024156 / RR / NCRR NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
NIH HL 46380 / HL / NHLBI NIH HHS / United States
N01-HC-45204 / HC / NHLBI NIH HHS / United States
5RC1HL099911-02 / HL / NHLBI NIH HHS / United States
NIDDK R01 2 DK078616 / / PHS HHS / United States
N01-HC-95095 / HC / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
N01-HC-48050 / HC / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
P20 MD006899 / MD / NIMHD NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01-HC-95169 / HC / NHLBI NIH HHS / United States
R01-HL-071205 / HL / NHLBI NIH HHS / United States
N01-HC-48049 / HC / NHLBI NIH HHS / United States
K24 DK080140 / DK / NIDDK NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
NIDDK K24 DK080140 / / PHS HHS / United States
N01-HC-95171 / HC / NHLBI NIH HHS / United States
N01HC95165-21-0-1 / HC / NHLBI NIH HHS / United States
N01-HC-95172 / HC / NHLBI NIH HHS / United States
N01-HC-95100 / HC / NHLBI NIH HHS / United States
N01-HD-95159 / HD / NICHD NIH HHS / United States
N01-HC-48048 / HC / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01-HC-95170 / HC / NHLBI NIH HHS / United States
N01-HC-65226 / HC / NHLBI NIH HHS / United States