Adiponectin Concentrations: A Genome-wide Association Study
Adiponectin Concentrations: A Genome-wide Association Study
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DOI：
10.1016/j.ajhg.2010.09.004
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发表时间：
2010-10-08
影响因子：
9.8
通讯作者：
Beaty, Terri H.
中科院分区：
文献类型：
--
作者：
Jee, Sun Ha;Sull, Jae Woong;Beaty, Terri H.
脂联素与肥胖和胰岛素抵抗有关。迄今为止，还没有亚洲人脂联素水平的全基因组关联研究（GWAS）。共4,001名受试者采用两阶段设计，使用全基因组标记物组进行基因分型（最初979名受试者，第二阶段3，022名受试者）另外2，304名受试者用于使用选定标记物的后续复制研究。在发现阶段，与脂联素平均对数相关的最高SNP是16号染色体上CDH 13中的rs3865188（在初始样品中p = 169 × 10（-15），在第二全基因组样品中p = 6.58 × 10（-39），在复制样品中p = 2.12 × 10（-32））。rs3865188在所有6，305名个体中的荟萃分析p值为2.82 × 10（-83）。rs3865188与高分子量脂联素的相关性（p = 7.36 × 10（-58））在第三个样本中甚至更强。一项报告基因分析评估了CDH 13启动子SNP在与rs3865188完全连锁不平衡中的作用，结果显示主要等位基因的表达增加了2.2倍。这项研究清楚地表明，CDH 13中的遗传变异影响韩国成年人的脂联素水平。
Adiponectin is associated with obesity and insulin resistance. To date, there has been no genome-wide association study (GWAS) of adiponectin levels in Asians Here we present a GWAS of a cohort of Korean volunteers. A total of 4,001 subjects were genotyped by using a genome-wide marker panel in a two-stage design (979 subjects initially and 3,022 in a second stage) Another 2,304 subjects were used for follow-up replication studies with selected markers In the discovery phase, the top SNP associated with mean log adiponectin was rs3865188 in CDH13 on chromosome 16 (p = 1 69 x 10(-15) in the initial sample, p = 6.58 x 10(-39) in the second genome-wide sample, and p = 2.12 x 10(-32) in the replication sample). The meta-analysis p value for rs3865188 in all 6,305 individuals was 2 82 x 10(-83) The association of rs3865188 with high-molecular-weight adiponectm (p = 7.36 x 10(-58)) was even stronger in the third sample. A reporter assay that evaluated the effects of a CDH13 promoter SNP in complete linkage disequilibrium with rs3865188 revealed that the major allele increased expression 2.2-fold This study clearly shows that genetic variants in CDH13 Influence adiponectm levels in Korean adults.