Clear detection of ADIPOQ locus as the major gene for plasma adiponectin: results of genome-wide association analyses including 4659 European individuals.
Clear detection of ADIPOQ locus as the major gene for plasma adiponectin: results of genome-wide association analyses including 4659 European individuals.
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DOI：
10.1016/j.atherosclerosis.2009.11.035
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发表时间：
2010-02
期刊：
影响因子：
5.3
通讯作者：
van Duijn, Cornelia M.
中科院分区：
文献类型：
--
作者：
Heid, Iris M.;Henneman, Peter;Hicks, Andrew;Coassin, Stefan;Winkler, Thomas;Aulchenko, Yurii S.;Fuchsberger, Christian;Song, Kijoung;Hivert, Marie-France;Waterworth, Dawn M.;Timpson, Nicholas J.;Richards, J. Brent;Perry, John R. B.;Tanaka, Toshiko;Amin, Najaf;Kollerits, Barbara;Pichler, Irene;Oostra, Ben A.;Thorand, Barbara;Frants, Rune R.;Illig, Thomas;Dupuis, Josee;Glaser, Beate;Spector, Tim;Guralnik, Jack;Egan, Josephine M.;Florez, Jose C.;Evans, David M.;Soranzo, Nicole;Bandinelli, Stefania;Carlson, Olga D.;Frayling, Timothy M.;Burling, Keith;Smith, George Davey;Mooser, Vincent;Ferrucci, Luigi;Meigs, James B.;Vollenweider, Peter;van Dijk, Ko Willems;Pramstaller, Peter;Kronenberg, Florian;van Duijn, Cornelia M.
血浆脂联素与代谢综合征、2型糖尿病和心血管结局的各种成分密切相关。浓度具有高度遗传性，男女之间存在差异。因此，我们的目的是调查男性和女性血浆脂联素的遗传学。我们结合了包括4659人的三项基于人群的研究的全基因组关联扫描。对于13795例受试者的复制阶段，我们选择了组合分析的20个最高信号，以及男性和女性特异性分析中p值小于1.0*10-4的10个最高信号。我们进一步选择了73个在以前的全基因组关联研究中与代谢综合征参数一致相关的SNP，以检查它们与血浆脂联素的关联。ADIPOQ基因座在组合分析（p=4.3*10-24）以及女性和男性特异性分析（分别为p=8.7*10-17和p=2.5*10-11）中显示全基因组显著p值。在复制分析中，其他39个最高信号SNP均未显示关联证据。代谢综合征基因座的73个SNPs均与血浆脂联素水平无关（p>0.01）。我们证明ADIPOQ基因是血浆脂联素的唯一主效基因，解释了6.7%的表型变异。我们进一步发现，无论是该基因还是任何代谢综合征位点都不能解释血浆脂联素的性别差异。需要更大规模的研究来确定血浆脂联素的更温和的遗传决定因素。
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. 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. 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). 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.
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