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

Publication ,  Journal Article
Liu, C-T; Ng, MCY; Rybin, D; Adeyemo, A; Bielinski, SJ; Boerwinkle, E; Borecki, I; Cade, B; Chen, YDI; Djousse, L; Fornage, M; Goodarzi, MO ...
Published in: Diabetologia
November 2012

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 <2, suggesting no recent positive selection. For 18 SNPs, all directions of effect were the same and 95% CIs of association overlapped when comparing EuA with AfA. For 17 of 18 loci, at least one SNP was nominally associated with FG in AfAs. Four loci were significantly associated with FG (GCK, p = 5.8 × 10(-8); MTNR1B, p = 8.5 × 10(-9); and FADS1, p = 2.2 × 10(-4)) or FI (GCKR, p = 5.9 × 10(-4)). At GCK and MTNR1B the EuA and AfA SNPs represented the same signal, while at FADS1, and GCKR, the EuA and best AfA SNPs were weakly correlated (r(2) <0.2), suggesting allelic heterogeneity for association with FG at these loci. 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.

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Published In

Diabetologia

DOI

EISSN

1432-0428

Publication Date

November 2012

Volume

55

Issue

11

Start / End Page

2970 / 2984

Location

Germany

Related Subject Headings

  • Young Adult
  • White People
  • Risk Factors
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Linkage Disequilibrium
  • Insulin
  • Hyperglycemia
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Liu, C.-T., Ng, M. C. Y., Rybin, D., Adeyemo, A., Bielinski, S. J., Boerwinkle, E., … Meigs, J. B. (2012). Transferability and fine-mapping of glucose and insulin quantitative trait loci across populations: CARe, the Candidate Gene Association Resource. Diabetologia, 55(11), 2970–2984. https://doi.org/10.1007/s00125-012-2656-4
Liu, C. -. T., M. C. Y. Ng, D. Rybin, A. Adeyemo, S. J. Bielinski, E. Boerwinkle, I. Borecki, et al. “Transferability and fine-mapping of glucose and insulin quantitative trait loci across populations: CARe, the Candidate Gene Association Resource.Diabetologia 55, no. 11 (November 2012): 2970–84. https://doi.org/10.1007/s00125-012-2656-4.
Liu C-T, Ng MCY, Rybin D, Adeyemo A, Bielinski SJ, Boerwinkle E, et al. Transferability and fine-mapping of glucose and insulin quantitative trait loci across populations: CARe, the Candidate Gene Association Resource. Diabetologia. 2012 Nov;55(11):2970–84.
Liu, C. .. T., et al. “Transferability and fine-mapping of glucose and insulin quantitative trait loci across populations: CARe, the Candidate Gene Association Resource.Diabetologia, vol. 55, no. 11, Nov. 2012, pp. 2970–84. Pubmed, doi:10.1007/s00125-012-2656-4.
Liu C-T, Ng MCY, 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. Transferability and fine-mapping of glucose and insulin quantitative trait loci across populations: CARe, the Candidate Gene Association Resource. Diabetologia. 2012 Nov;55(11):2970–2984.
Journal cover image

Published In

Diabetologia

DOI

EISSN

1432-0428

Publication Date

November 2012

Volume

55

Issue

11

Start / End Page

2970 / 2984

Location

Germany

Related Subject Headings

  • Young Adult
  • White People
  • Risk Factors
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Linkage Disequilibrium
  • Insulin
  • Hyperglycemia