A meta-analysis of genome-wide association studies for adiponectin levels in East Asians identifies a novel locus near WDR11-FGFR2
Journal
Human Molecular Genetics
Journal Volume
23
Journal Issue
4
Pages
1108-1119
Date Issued
2014
Author(s)
Wu Y.
Gao H.
Li H.
Tabara Y.
Nakatochi M.
Chiu Y.-F.
Park E.J.
Wen W.
Adair L.S.
Borja J.B.
Cai Q.
Chen P.
Croteau-Chonka D.C.
Fogarty M.P.
Gan W.
He C.-T.
Hsiung C.A.
Hwu C.-M.
Ichihara S.
Igase M.
Jo J.
Kato N.
Kawamoto R.
Kuzawa C.W.
Lee J.J.M.
Liu J.
Lu L.
Mcdade T.W.
Osawa H.
Sheu W.H.-H.
Teo Y.
Vadlamudi S.
Van Dam R.M.
Wang Y.
Xiang Y.-B.
Yamamoto K.
Ye X.
Young T.L.
Zheng W.
Zhu J.
Shu X.-O.
Shin C.
Jee S.H.
Miki T.
Yokota M.
Lin X.
Mohlke K.L.
Tai E.S.
Abstract
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 adiponectinassociated 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. ? The Author 2013. Published by Oxford University Press. All rights reserved.
SDGs
Other Subjects
adiponectin; fibroblast growth factor receptor 2; G protein coupled receptor 109a; high density lipoprotein cholesterol; proline dipeptidase; protein; transcription factor c Maf; triacylglycerol; unclassified drug; wdr11 protein; zinc finger protein 664; article; Asian; body mass; cell hyperplasia; cholesterol blood level; chromosome 10; chromosome 12; chromosome 16; computer model; DNA flanking region; follow up; gene locus; genetic analysis; genetic association; genetic trait; genotype; human; meta analysis; obesity; priority journal; single nucleotide polymorphism; triacylglycerol blood level; waist hip ratio; Adiponectin; Asian Continental Ancestry Group; Cardiovascular Diseases; Cohort Studies; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Membrane Proteins; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins; Receptor, Fibroblast Growth Factor, Type 2
Type
journal article