title: Clear detection of ADIPOQ locus as the major gene for plasma adiponectin: results of genome-wide association analyses including 4659 European individuals.
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 x 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 x 10(-24)) as well as in both women- and men-specific analyses (p=8.7 x 10(-17) and p=2.5 x 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.
authors.affiliation: Department of Epidemiology and Preventive Medicine, Regensburg University Medical Center, Regensburg, Germany.
authors.forename: Iris M
authors.initials: IM
authors.lastname: Heid
authors.forename: Peter
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authors.lastname: Henneman
authors.forename: Andrew
authors.initials: A
authors.lastname: Hicks
authors.forename: Stefan
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authors.lastname: Coassin
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authors.lastname: Winkler
authors.forename: Yurii S
authors.initials: YS
authors.lastname: Aulchenko
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authors.lastname: Fuchsberger
authors.forename: Kijoung
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authors.lastname: Song
authors.forename: Marie-France
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authors.lastname: Hivert
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Waterworth
authors.forename: Nicholas J
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authors.forename: J Brent
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authors.lastname: Richards
authors.forename: John R B
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authors.forename: Toshiko
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authors.lastname: Kollerits
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authors.lastname: Pichler
authors.forename: Ben A
authors.initials: BA
authors.lastname: Oostra
authors.forename: Barbara
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authors.lastname: Thorand
authors.forename: Rune R
authors.initials: RR
authors.lastname: Frants
authors.forename: Thomas
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authors.lastname: Illig
authors.forename: Josée
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authors.lastname: Dupuis
authors.forename: Beate
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authors.lastname: Glaser
authors.forename: Tim
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authors.lastname: Spector
authors.forename: Jack
authors.initials: J
authors.lastname: Guralnik
authors.forename: Josephine M
authors.initials: JM
authors.lastname: Egan
authors.forename: Jose C
authors.initials: JC
authors.lastname: Florez
authors.forename: David M
authors.initials: DM
authors.lastname: Evans
authors.forename: Nicole
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authors.lastname: Soranzo
authors.forename: Stefania
authors.initials: S
authors.lastname: Bandinelli
authors.forename: Olga D
authors.initials: OD
authors.lastname: Carlson
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Frayling
authors.forename: Keith
authors.initials: K
authors.lastname: Burling
authors.forename: George Davey
authors.initials: GD
authors.lastname: Smith
authors.forename: Vincent
authors.initials: V
authors.lastname: Mooser
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: James B
authors.initials: JB
authors.lastname: Meigs
authors.forename: Peter
authors.initials: P
authors.lastname: Vollenweider
authors.forename: Ko Willems van
authors.initials: KW
authors.lastname: Dijk
authors.forename: Peter
authors.initials: P
authors.lastname: Pramstaller
authors.forename: Florian
authors.initials: F
authors.lastname: Kronenberg
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
mesh_terms: D052242:Adiponectin / Q000097:blood; D002318:Cardiovascular Diseases / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D005060:Europe; D005260:Female; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin