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Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

Publication ,  Journal Article
Dastani, Z; Hivert, M-F; Timpson, N; Perry, JRB; Yuan, X; Scott, RA; Henneman, P; Heid, IM; Kizer, JR; Lyytikäinen, L-P; Fuchsberger, C; Qi, L ...
Published in: PLoS Genet
2012

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.

Duke Scholars

Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

2012

Volume

8

Issue

3

Start / End Page

e1002607

Location

United States

Related Subject Headings

  • White People
  • Waist-Hip Ratio
  • Polymorphism, Single Nucleotide
  • Metabolic Networks and Pathways
  • Male
  • Insulin Resistance
  • Humans
  • Glucose Tolerance Test
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
 

Citation

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Chicago
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Dastani, Z., Hivert, M.-F., Timpson, N., Perry, J. R. B., Yuan, X., Scott, R. A., … Nieminen, M. S. (2012). Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals. PLoS Genet, 8(3), e1002607. https://doi.org/10.1371/journal.pgen.1002607
Dastani, Zari, Marie-France Hivert, Nicholas Timpson, John R. B. Perry, Xin Yuan, Robert A. Scott, Peter Henneman, et al. “Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.PLoS Genet 8, no. 3 (2012): e1002607. https://doi.org/10.1371/journal.pgen.1002607.
Dastani Z, Hivert M-F, Timpson N, Perry JRB, Yuan X, Scott RA, et al. Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals. PLoS Genet. 2012;8(3):e1002607.
Dastani, Zari, et al. “Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.PLoS Genet, vol. 8, no. 3, 2012, p. e1002607. Pubmed, doi:10.1371/journal.pgen.1002607.
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D, Boehnke M, McCarthy MI, Soranzo N, Wheeler E, Glazer NL, Bouatia-Naji N, Mägi R, Randall J, Elliott P, Rybin D, Dehghan A, Hottenga JJ, Song K, Goel A, Lajunen T, Doney A, Cavalcanti-Proença C, Kumari M, Timpson NJ, Zabena C, Ingelsson E, An P, O’Connell J, Luan J, Elliott A, Roccasecca RM, Pattou F, Sethupathy P, Ariyurek Y, Barter P, Beilby JP, Ben-Shlomo Y, Bergmann S, Bochud M, Bonnefond A, Borch-Johnsen K, Böttcher Y, Brunner E, Bumpstead SJ, Chen Y-DI, Chines P, Clarke R, Coin LJM, Cooper MN, Crisponi L, Day INM, de Geus EJC, Delplanque J, Fedson AC, Fischer-Rosinsky A, Forouhi NG, Franzosi MG, Galan P, Goodarzi MO, Graessler J, Grundy S, Gwilliam R, Hallmans G, Hammond N, Han X, Hartikainen A-L, Hayward C, Heath SC, Hercberg S, Hillman DR, Hingorani AD, Hui J, Hung J, Kaakinen M, Kaprio J, Kesaniemi YA, Kivimaki M, Knight B, Koskinen S, Kovacs P, Kyvik KO, Lathrop GM, Lawlor DA, Le Bacquer O, Lecoeur C, Li Y, Mahley R, Mangino M, Martínez-Larrad MT, McAteer JB, McPherson R, 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Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals. PLoS Genet. 2012;8(3):e1002607.

Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

2012

Volume

8

Issue

3

Start / End Page

e1002607

Location

United States

Related Subject Headings

  • White People
  • Waist-Hip Ratio
  • Polymorphism, Single Nucleotide
  • Metabolic Networks and Pathways
  • Male
  • Insulin Resistance
  • Humans
  • Glucose Tolerance Test
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease