...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>PLoS Genetics >A Genome-Wide Association Study Reveals Variants in ARL15 that Influence Adiponectin Levels
【24h】

A Genome-Wide Association Study Reveals Variants in ARL15 that Influence Adiponectin Levels

机译：全基因组关联研究揭示了影响脂联素水平的ARL15变异。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The adipocyte-derived protein adiponectin is highly heritable and inversely associated with risk of type 2 diabetes mellitus (T2D) and coronary heart disease (CHD). We meta-analyzed 3 genome-wide association studies for circulating adiponectin levels (n?=?8,531) and sought validation of the lead single nucleotide polymorphisms (SNPs) in 5 additional cohorts (n?=?6,202). Five SNPs were genome-wide significant in their relationship with adiponectin (P≤5×10?8). We then tested whether these 5 SNPs were associated with risk of T2D and CHD using a Bonferroni-corrected threshold of P≤0.011 to declare statistical significance for these disease associations. SNPs at the adiponectin-encoding ADIPOQ locus demonstrated the strongest associations with adiponectin levels (P-combined?=?9.2×10?19 for lead SNP, rs266717, n?=?14,733). A novel variant in the ARL15 (ADP-ribosylation factor-like 15) gene was associated with lower circulating levels of adiponectin (rs4311394-G, P-combined?=?2.9×10?8, n?=?14,733). This same risk allele at ARL15 was also associated with a higher risk of CHD (odds ratio [OR]?=?1.12, P?=?8.5×10?6, n?=?22,421) more nominally, an increased risk of T2D (OR?=?1.11, P?=?3.2×10?3, n?=?10,128), and several metabolic traits. Expression studies in humans indicated that ARL15 is well-expressed in skeletal muscle. These findings identify a novel protein, ARL15, which influences circulating adiponectin levels and may impact upon CHD risk.
机译：脂肪细胞衍生的脂联素是高度可遗传的，并且与2型糖尿病（T2D）和冠心病（CHD）的风险成反比。我们对循环脂联素水平（n == 8,531）进行了3个全基因组关联研究的荟萃分析，并试图在另外5个队列（n == 6202）中验证先导单核苷酸多态性（SNP）。 5个SNP与脂联素的关系在全基因组中具有显着性（P≤5×10？8）。然后，我们使用Bonferroni校正的P≤0.011阈值测试了这5个SNP是否与T2D和CHD风险相关，以声明这些疾病相关的统计学意义。编码脂连蛋白的ADIPOQ基因座处的SNP显示出与脂连蛋白水平的最强关联（铅SNP的P-组合β＝≥9.2×10≤19，rs266717，nα＝≥14,733）。 ARL15（ADP-核糖基化因子样15）基因中的新变体与脂联素的较低循环水平有关（rs4311394-G，P-结合的α＝β2.9×10β8，nα＝α14,733）。在ARL15处，相同风险等位基因还与冠心病的更高风险相关（奇数比[OR]？=？1.12，P？=？8.5×10？6，n？=？22,421），T2D的风险增加。 （OR ＝＝ 1.11，P ＝＝ 3.2×10 ＝ 3，n ＝＝ 10,128），以及一些代谢性状。在人中的表达研究表明，ARL15在骨骼肌中表达良好。这些发现确定了一种新型蛋白质ARL15，该蛋白质会影响循环脂联素水平并可能影响冠心病风险。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号