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A meta-analysis of genome-wide association studies for adiponectin levels in East Asians identifies a novel locus near WDR11-FGFR2.

Publication ,  Journal Article
Wu, Y; Gao, H; Li, H; Tabara, Y; Nakatochi, M; Chiu, Y-F; Park, EJ; Wen, W; Adair, LS; Borja, JB; Cai, Q; Chang, Y-C; Chen, P; Fogarty, MP ...
Published in: Hum Mol Genet
February 15, 2014

Blood levels of adiponectin, an adipocyte-secreted protein correlated with metabolic and cardiovascular risks, are highly heritable. Genome-wide association (GWA) studies for adiponectin levels have identified 14 loci harboring variants associated with blood levels of adiponectin. To identify novel adiponectin-associated loci, particularly those of importance in East Asians, we conducted a meta-analysis of GWA studies for adiponectin in 7827 individuals, followed by two stages of replications in 4298 and 5954 additional individuals. We identified a novel adiponectin-associated locus on chromosome 10 near WDR11-FGFR2 (P = 3.0 × 10(-14)) and provided suggestive evidence for a locus on chromosome 12 near OR8S1-LALBA (P = 1.2 × 10(-7)). Of the adiponectin-associated loci previously described, we confirmed the association at CDH13 (P = 6.8 × 10(-165)), ADIPOQ (P = 1.8 × 10(-22)), PEPD (P = 3.6 × 10(-12)), CMIP (P = 2.1 × 10(-10)), ZNF664 (P = 2.3 × 10(-7)) and GPR109A (P = 7.4 × 10(-6)). Conditional analysis at ADIPOQ revealed a second signal with suggestive evidence of association only after conditioning on the lead SNP (Pinitial = 0.020; Pconditional = 7.0 × 10(-7)). We further confirmed the independence of two pairs of closely located loci (<2 Mb) on chromosome 16 at CMIP and CDH13, and on chromosome 12 at GPR109A and ZNF664. In addition, the newly identified signal near WDR11-FGFR2 exhibited evidence of association with triglycerides (P = 3.3 × 10(-4)), high density lipoprotein cholesterol (HDL-C, P = 4.9 × 10(-4)) and body mass index (BMI)-adjusted waist-hip ratio (P = 9.8 × 10(-3)). These findings improve our knowledge of the genetic basis of adiponectin variation, demonstrate the shared allelic architecture for adiponectin with lipids and central obesity and motivate further studies of underlying mechanisms.

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Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

February 15, 2014

Volume

23

Issue

4

Start / End Page

1108 / 1119

Location

England

Related Subject Headings

  • Receptor, Fibroblast Growth Factor, Type 2
  • Proto-Oncogene Proteins
  • Polymorphism, Single Nucleotide
  • Membrane Proteins
  • Humans
  • Genome-Wide Association Study
  • Genetics & Heredity
  • Genetic Predisposition to Disease
  • Genetic Loci
  • Cohort Studies
 

Citation

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Wu, Y., Gao, H., Li, H., Tabara, Y., Nakatochi, M., Chiu, Y.-F., … Tai, E. S. (2014). A meta-analysis of genome-wide association studies for adiponectin levels in East Asians identifies a novel locus near WDR11-FGFR2. Hum Mol Genet, 23(4), 1108–1119. https://doi.org/10.1093/hmg/ddt488
Wu, Ying, He Gao, Huaixing Li, Yasuharu Tabara, Masahiro Nakatochi, Yen-Feng Chiu, Eun Jung Park, et al. “A meta-analysis of genome-wide association studies for adiponectin levels in East Asians identifies a novel locus near WDR11-FGFR2.Hum Mol Genet 23, no. 4 (February 15, 2014): 1108–19. https://doi.org/10.1093/hmg/ddt488.
Wu Y, Gao H, Li H, Tabara Y, Nakatochi M, Chiu Y-F, et al. A meta-analysis of genome-wide association studies for adiponectin levels in East Asians identifies a novel locus near WDR11-FGFR2. Hum Mol Genet. 2014 Feb 15;23(4):1108–19.
Wu, Ying, et al. “A meta-analysis of genome-wide association studies for adiponectin levels in East Asians identifies a novel locus near WDR11-FGFR2.Hum Mol Genet, vol. 23, no. 4, Feb. 2014, pp. 1108–19. Pubmed, doi:10.1093/hmg/ddt488.
Wu Y, Gao H, Li H, Tabara Y, Nakatochi M, Chiu Y-F, Park EJ, Wen W, Adair LS, Borja JB, Cai Q, Chang Y-C, Chen P, Croteau-Chonka DC, Fogarty MP, Gan W, He C-T, Hsiung CA, Hwu C-M, Ichihara S, Igase M, Jo J, Kato N, Kawamoto R, Kuzawa CW, Lee JJM, Liu J, Lu L, McDade TW, Osawa H, Sheu WH-H, Teo Y, Vadlamudi S, Van Dam RM, Wang Y, Xiang Y-B, Yamamoto K, Ye X, Young TL, Zheng W, Zhu J, Shu X-O, Shin C, Jee SH, Chuang L-M, Miki T, Yokota M, Lin X, Mohlke KL, Tai ES. A meta-analysis of genome-wide association studies for adiponectin levels in East Asians identifies a novel locus near WDR11-FGFR2. Hum Mol Genet. 2014 Feb 15;23(4):1108–1119.
Journal cover image

Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

February 15, 2014

Volume

23

Issue

4

Start / End Page

1108 / 1119

Location

England

Related Subject Headings

  • Receptor, Fibroblast Growth Factor, Type 2
  • Proto-Oncogene Proteins
  • Polymorphism, Single Nucleotide
  • Membrane Proteins
  • Humans
  • Genome-Wide Association Study
  • Genetics & Heredity
  • Genetic Predisposition to Disease
  • Genetic Loci
  • Cohort Studies