Section on Statistical Genetics, Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.
Hum Genomics. 2011 Jan;5(2):79-89. doi: 10.1186/1479-7364-5-2-79.
Type 2 diabetes represents an increasing health burden. Its prevalence is rising among younger age groups and differs among racial/ethnic groups. Little is known about its genetic basis, including whether there is a genetic basis for racial/ethnic disparities. We examined a multi-ethnic sample of 253 healthy children to evaluate associations between insulin-related phenotypes and 142 ancestry-informative markers (AIMs), while adjusting for sex, age, Tanner stage, genetic admixture, total body fat, height and socio-economic status. We also evaluated the effect of measurement errors in the estimation of the individual ancestry proportions on the regression results. We found that European genetic admixture is positively associated with insulin sensitivity (S I ), and negatively associated with the acute insulin response to glucose, fasting insulin levels and the homeostasis model assessment of insulin resistance. Our analysis revealed associations between individual AIMs on chromosomes 2, 8 and 15 and these phenotypes. Most notably, marker rs3287 at chromosome 2p21 was found to be associated with S I ( p = 5.8 × 10(-5)). This marker may be in admixture linkage disequilibrium with nearby loci ( THADA and BCL11A ) that previously have been reported to be associated with diabetes and diabetes-related phenotypes in several genome-wide association and linkage studies. Our results provide further evidence that variation in the 2p21 region containing THADA and BCL11A is associated with type 2 diabetes. Importantly, we have implicated this region in the early development of diabetes-related phenotypes, and in the genetic aetiology of population differences in these phenotypes.
2 型糖尿病代表着日益加重的健康负担。其在年轻人群中的发病率正在上升，且在不同种族/民族群体间存在差异。其遗传基础知之甚少，包括种族/民族差异是否存在遗传基础。我们检查了一个多民族的 253 名健康儿童的样本，以评估胰岛素相关表型与 142 个种族来源信息标记（AIMs）之间的关联，同时调整性别、年龄、性发育阶段、遗传混合程度、体脂肪总量、身高和社会经济地位。我们还评估了个体种族比例估计中的测量误差对回归结果的影响。我们发现，欧洲遗传混合程度与胰岛素敏感性（S I）呈正相关，与葡萄糖急性胰岛素反应、空腹胰岛素水平和胰岛素抵抗的稳态模型评估呈负相关。我们的分析显示，2、8 和 15 号染色体上的单个 AIMs 与这些表型之间存在关联。值得注意的是，染色体 2p21 上的标记 rs3287 与 S I 相关（p=5.8×10(-5)）。该标记可能与附近的基因座（THADA 和 BCL11A）处于混合连锁不平衡状态，这些基因座之前在多个全基因组关联和连锁研究中被报道与糖尿病和糖尿病相关表型有关。我们的结果进一步证明，包含 THADA 和 BCL11A 的 2p21 区域的变异与 2 型糖尿病有关。重要的是，我们已经表明该区域与糖尿病相关表型的早期发展以及这些表型在人群中的遗传病因有关。
