Clear detection of ADIPOQ locus as the major gene for plasma adiponectin: Results of genome-wide association analyses including 4659 European individuals

Iris M. Heid, Peter Henneman, Andrew Hicks, Stefan Coassin, Thomas Winkler, Yurii S. Aulchenko, Christian Fuchsberger, Kijoung Song, Marie France Hivert, Dawn M. Waterworth, Nicholas J. Timpson, J. Brent Richards, John R B Perry, Toshiko Tanaka, Najaf Amin, Barbara Kollerits, Irene Pichler, Ben A. Oostra, Barbara Thorand, Rune R. FrantsThomas Illig, Josée Dupuis, Beate Glaser, Tim Spector, Jack Guralnik, Josephine M. Egan, Jose C. Florez, David M. Evans, Nicole Soranzo, Stefania Bandinelli, Olga D. Carlson, Timothy M. Frayling, Keith Burling, George Davey Smith, Vincent Mooser, Luigi Ferrucci, James B. Meigs, Peter Vollenweider, Ko Willems van Dijk, Peter Pramstaller, Florian Kronenberg, Cornelia M. van Duijn

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Plasma adiponectin is strongly associated with various components of metabolic syndrome, type 2 diabetes and cardiovascular outcomes. Concentrations are highly heritable and differ between men and women. We therefore aimed to investigate the genetics of plasma adiponectin in men and women. Methods: We combined genome-wide association scans of three population-based studies including 4659 persons. For the replication stage in 13795 subjects, we selected the 20 top signals of the combined analysis, as well as the 10 top signals with p-values less than 1.0 × 10-4 for each the men- and the women-specific analyses. We further selected 73 SNPs that were consistently associated with metabolic syndrome parameters in previous genome-wide association studies to check for their association with plasma adiponectin. Results: The ADIPOQ locus showed genome-wide significant p-values in the combined (p = 4.3 × 10-24) as well as in both women- and men-specific analyses (p = 8.7 × 10-17 and p = 2.5 × 10-11, respectively). None of the other 39 top signal SNPs showed evidence for association in the replication analysis. None of 73 SNPs from metabolic syndrome loci exhibited association with plasma adiponectin (p > 0.01). Conclusions: We demonstrated the ADIPOQ gene as the only major gene for plasma adiponectin, which explains 6.7% of the phenotypic variance. We further found that neither this gene nor any of the metabolic syndrome loci explained the sex differences observed for plasma adiponectin. Larger studies are needed to identify more moderate genetic determinants of plasma adiponectin.

Original languageEnglish (US)
Pages (from-to)412-420
Number of pages9
JournalAtherosclerosis
Volume208
Issue number2
DOIs
StatePublished - Feb 2010
Externally publishedYes

Keywords

  • Adiponectin
  • Cardiovascular disease
  • Genome-wide association study
  • Metabolic syndrome
  • Polymorphism

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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