A meta-analysis of genome-wide association studies for adiponectin levels in East Asians identifies a novel locus near WDR11-FGFR2.
A meta-analysis of genome-wide association studies for adiponectin levels in East Asians identifies a novel locus near WDR11-FGFR2.
复制标题
DOI：
10.1093/hmg/ddt488
复制
发表时间：
2014-02
影响因子：
3.5
通讯作者：
Ying Wu;He Gao;He Gao;Huaixing Li;Y. Tabara;M. Nakatochi;Y. Chiu;Y. Chiu;Eun Jung Park
中科院分区：
文献类型：
--
作者：
Ying Wu;He Gao;He Gao;Huaixing Li;Y. Tabara;M. Nakatochi;Y. Chiu;Y. Chiu;Eun Jung Park
脂联素是一种脂肪细胞分泌的蛋白质，与代谢和心血管风险相关，其血液水平具有高度遗传性。脂联素水平的全基因组关联（GWA）研究已经确定了14个基因座，这些基因座含有与脂联素血液水平相关的变异。为了确定新的脂联素相关基因座，特别是那些在东亚人中具有重要意义的基因座，我们对7827名个体的脂联素GWA研究进行了荟萃分析，然后在另外4298和5954名个体中进行了两个阶段的重复研究。我们在10号染色体上WDR 11-FGFR 2附近发现了一个新的脂联素相关位点（P = 3.0 × 10（-14）），并为12号染色体上OR 8 S1-LALBA附近的一个位点（P = 1.2 × 10（-7））提供了提示性证据。在先前描述的脂联素相关位点中，我们证实了CDH 13位点的相关性（P = 6.8 × 10（-165）），ADIPOQ（P = 1.8 × 10（-22））、PEPD（P = 3.6 × 10（-12））、CMIP（P = 2.1 × 10（-10））、ZNF 664（P = 2.3 × 10（-7））和GPR 109A（P = 7.4 × 10（-6））。ADIPOQ的条件分析揭示了第二个信号，只有在以前导SNP为条件后才有关联的提示证据（P初始= 0.020; P条件= 7.0 × 10（-7））。进一步证实了16号染色体上CMIP和CDH 13以及12号染色体上GPR 109 A和ZNF 664两对近距离定位的基因座（<2 Mb）的独立性。此外，新发现的WDR 11-FGFR 2附近的信号显示与甘油三酯（P = 3.3 × 10（-4））、高密度脂蛋白胆固醇（HDL-C，P = 4.9 × 10（-4））和体重指数（BMI）调整的腰臀比（P = 9.8 × 10（-3））相关的证据。这些发现提高了我们对脂联素变异的遗传基础的认识，证明了脂联素与血脂和中心性肥胖共享的等位基因结构，并激发了对潜在机制的进一步研究。
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 WDR11-FGFR2 (P = 3.0 × 10(-14)) and provided suggestive evidence for a locus on chromosome 12 near OR8S1-LALBA (P = 1.2 × 10(-7)). Of the adiponectin-associated loci previously described, we confirmed the association at CDH13 (P = 6.8 × 10(-165)), ADIPOQ (P = 1.8 × 10(-22)), PEPD (P = 3.6 × 10(-12)), CMIP (P = 2.1 × 10(-10)), ZNF664 (P = 2.3 × 10(-7)) and GPR109A (P = 7.4 × 10(-6)). Conditional analysis at ADIPOQ revealed a second signal with suggestive evidence of association only after conditioning on the lead SNP (Pinitial = 0.020; Pconditional = 7.0 × 10(-7)). We further confirmed the independence of two pairs of closely located loci (<2 Mb) on chromosome 16 at CMIP and CDH13, and on chromosome 12 at GPR109A and ZNF664. In addition, the newly identified signal near WDR11-FGFR2 exhibited evidence of association with triglycerides (P = 3.3 × 10(-4)), high density lipoprotein cholesterol (HDL-C, P = 4.9 × 10(-4)) and body mass index (BMI)-adjusted waist-hip ratio (P = 9.8 × 10(-3)). 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.