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

Heid, I.M.; Henneman, P.; Hicks, A.; Coassin, S.; Winkler, T.; Aulchenko, Y.S.; Fuchsberger, C.; Song, K.; Hivert, M.F.; Waterworth, D.M.; Timpson, N.J.; Richards, J.B.; Perry, J.R.B.; Tanaka, T.; Amin, N.; Kollerits, B.; Pichler, I.; Oostra, B.A.; Thorand, B.; Frants, R.R.; Illig, T.; Dupuis, J.; Glaser, B.; Spector, T.; Guralnik, J.; Egan, J.M.; Florez, J.C.; Evans, D.M.; Soranzo, N.; Bandinelli, S.; Carlson, O.D.; Frayling, T.M.; Burling, K.; Smith, G.D.; Mooser, V.; Ferrucci, L.; Meigs, J.B.; Vollenweider, P.; Dijk, K.W. van; Pramstaller, P.; Kronenberg, F.; Duijn, C.M. van

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: Wecombined 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)...Show moreObjective: 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: Wecombined 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 e x hibited association with plasma adiponectin (p > 0.01). Conclusions: We demonstrated the ADIPOQ gene as the only major gene for plasma adiponectin, which e x plains 6.7% of the phenotypic variance. We further found that neither this gene nor any of the metabolic syndrome loci e x plained the se x differences observed for plasma adiponectin. Larger studies are needed to identify more moderate genetic determinants of plasma adiponectin. (C) 2009 Elsevier Ireland Ltd. All rights reserved.Show less

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