Title | Transferability and fine-mapping of glucose and insulin quantitative trait loci across populations: CARe, the Candidate Gene Association Resource. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Liu 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, Meigs JB |
Journal | Diabetologia |
Volume | 55 |
Issue | 11 |
Pagination | 2970-84 |
Date Published | 2012 Nov |
ISSN | 1432-0428 |
Keywords | Adult, African Americans, Aged, Aged, 80 and over, Blood Glucose, Databases, Genetic, Delta-5 Fatty Acid Desaturase, Diabetes Mellitus, Type 2, Female, Gene Frequency, Genetic Predisposition to Disease, Humans, Hyperglycemia, Insulin, Linkage Disequilibrium, Male, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Risk Factors, Whites, 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. |
DOI | 10.1007/s00125-012-2656-4 |
Alternate Journal | Diabetologia |
PubMed ID | 22893027 |
PubMed Central ID | PMC3804308 |
Grant List | R01 DK078616 / DK / NIDDK 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-55022 / HC / NHLBI NIH HHS / United States NIDDK R01 2 DK078616 / / PHS HHS / United States N01-HC-48050 / HC / NHLBI NIH HHS / United States P20 MD006899 / MD / NIMHD NIH HHS / United States N01-HC-55020 / HC / NHLBI NIH HHS / United States N01-HC-95100 / HC / NHLBI NIH HHS / United States N01-HC-95170 / HC / NHLBI NIH HHS / United States N01-HC-65226 / HC / NHLBI NIH HHS / United States 5UC2HL103010-02 / HL / NHLBI NIH HHS / United States N01-HC-45205 / HC / NHLBI NIH HHS / United States N01-HC-48047 / HC / NHLBI NIH HHS / United States M01RR00080 / RR / NCRR 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 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 P30 DK063491 / DK / NIDDK NIH HHS / United States N01-HC-55019 / HC / NHLBI 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 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-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 |