Cha Seongwon, Park Ah Yeon, Kang Changsoo
Mibyeong Research Center, Korea Institute of Oriental Medicine, 1672 Yuseongdae-ro, Yuseong-gu, Daejeon 34054, Republic of Korea.
Department of Biology and Research Institute of Basic Sciences, College of Natural Sciences, Sungshin Women's University, Seoul, 01133, Republic of Korea.
PLoS One. 2015 Dec 16;10(12):e0145220. doi: 10.1371/journal.pone.0145220. eCollection 2015.
The thoracic-to-hip circumference ratio (THR) is an anthropometric marker recently described as a predictor of type 2 diabetes. In this study, we performed a genome-wide association study (GWAS) followed by confirmatory analyses to identify genetic markers associated with THR. A total of 7,240 Korean subjects (4,988 for the discovery stage and 2,252 for the confirmatory analyses) were recruited for this study, and genome-wide single nucleotide polymorphism (SNP) genotyping of the initial 4,988 individuals was performed using Affymetrix Human SNP array 5.0. Linear regression analysis was then performed to adjust for the effects of age, sex, and current diabetes medication status on the THR of the study subjects. In the initial discovery stage, there was a statistically nominal association between minor alleles of SNP markers on chromosomes 4, 8, 10, and 12, and THR changes (p < 5.0 × 10-6). The subsequent confirmatory analyses of these markers, however, only detected a significant association between two SNPs in the HECTD4 gene and decreased THRs. Notably, this association was detected in male (rs11066280: p = 1.14 × 10-2; rs2074356: p = 1.10 × 10-2), but not in female subjects. Meanwhile, the combined results from the two analyses (initial and confirmatory) indicated that minor alleles of these two intronic variants exhibited a significant genome-wide association with decreased THR in the male subjects (n = 3,155; rs11066280: effect size = -0.008624, p = 6.19 × 10-9; rs2074356: effect size = -0.008762, p = 1.89 × 10-8). Furthermore, minor alleles of these two SNPs exhibited protective effects on patients' risks for developing type 2 diabetes. In conclusion, we have identified two genetic variations in HECTD4 that are associated with THR, particularly in men.
胸臀围比（THR）是一种人体测量指标，最近被描述为2型糖尿病的预测指标。在本研究中，我们进行了全基因组关联研究（GWAS），随后进行了验证性分析，以确定与THR相关的遗传标记。本研究共招募了7240名韩国受试者（发现阶段4988名，验证性分析阶段2252名），并使用Affymetrix Human SNP array 5.0对最初的4988名个体进行了全基因组单核苷酸多态性（SNP）基因分型。然后进行线性回归分析，以调整年龄、性别和当前糖尿病用药状态对研究对象THR的影响。在最初的发现阶段，4号、8号、10号和12号染色体上SNP标记的次要等位基因与THR变化之间存在统计学上的名义关联（p < 5.0 × 10-6）。然而，对这些标记的后续验证性分析仅检测到HECTD4基因中的两个SNP与THR降低之间存在显著关联。值得注意 的是，这种关联在男性中被检测到（rs11066280：p = 1.14 × 10-2；rs2074356：p = 1.10 × 10-2），但在女性受试者中未被检测到。同时，两项分析（初始分析和验证性分析）的综合结果表明，这两个内含子变异的次要等位基因在男性受试者（n = 3155；rs11066280：效应大小 = -0.008624，p = 6.19 × 10-9；rs2074356：效应大小 = -0.008762，p = 1.89 × 10-8）中与THR降低呈现出显著的全基因组关联。此外，这两个SNP的次要等位基因对患者患2型糖尿病的风险具有保护作用。总之，我们在HECTD4中鉴定出两个与THR相关的遗传变异，尤其是在男性中。
