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- 저자 : Nakatochi, Masahiro (검색결과 1 건)
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Wu, Ying,Gao, He,Li, Huaixing,Tabara, Yasuharu,Nakatochi, Masahiro,Chiu, Yen-Feng,Park, Eun Jung,Wen, Wanqing,Adair, Linda S.,Borja, Judith B.,Cai, Qiuyin,Chang, Yi-Cheng,Chen, Peng,Croteau-Chonka, Da Oxford University Press 2014 Human Molecular Genetics Vol.23 No.4
<P>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 <I>WDR11-FGFR2</I> (<I>P</I> = 3.0 × 10<SUP>−14</SUP>) and provided suggestive evidence for a locus on chromosome 12 near <I>OR8S1-LALBA</I> (<I>P</I> = 1.2 × 10<SUP>−7</SUP>). Of the adiponectin-associated loci previously described, we confirmed the association at <I>CDH13</I> (<I>P</I> = 6.8 × 10<SUP>−165</SUP>), <I>ADIPOQ</I> (<I>P</I> = 1.8 × 10<SUP>−22</SUP>), <I>PEPD</I> (<I>P</I> = 3.6 × 10<SUP>−12</SUP>), <I>CMIP</I> (<I>P</I> = 2.1 × 10<SUP>−10</SUP>), <I>ZNF664</I> (<I>P</I> = 2.3 × 10<SUP>−7</SUP>) and <I>GPR109A</I> (<I>P</I> = 7.4 × 10<SUP>−6</SUP>). Conditional analysis at <I>ADIPOQ</I> revealed a second signal with suggestive evidence of association only after conditioning on the lead SNP (<I>P</I><SUB>initial</SUB> = 0.020; <I>P</I><SUB>conditional</SUB> = 7.0 × 10<SUP>−7</SUP>). We further confirmed the independence of two pairs of closely located loci (<2 Mb) on chromosome 16 at <I>CMIP</I> and <I>CDH13</I>, and on chromosome 12 at <I>GPR109A</I> and <I>ZNF664</I>. In addition, the newly identified signal near <I>WDR11-FGFR2</I> exhibited evidence of association with triglycerides (<I>P</I> = 3.3 × 10<SUP>−4</SUP>), high density lipoprotein cholesterol (HDL-C, <I>P</I> = 4.9 × 10<SUP>−4</SUP>) and body mass index (BMI)-adjusted waist–hip ratio (<I>P</I> = 9.8 × 10<SUP>−3</SUP>). 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.</P>
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