Department of Internal Medicine, National Taiwan University Hospital HsinChu branch, Taipei, Taiwan; Institute of Biomedical Science, Academia Sinica, Taipei, Taiwan.
Clinical Informatics and Medical Statistics Research Center, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
PLoS One. 2014 Apr 15;9(4):e95045. doi: 10.1371/journal.pone.0095045. eCollection 2014.
Several genome-wide association studies (GWAS) involving European populations have successfully identified risk genetic variants associated with type 2 diabetes mellitus (T2DM). However, the effects conferred by these variants in Han Chinese population have not yet been fully elucidated.
We analyzed the effects of 24 risk genetic variants with reported associations from European GWAS in 3,040 Han Chinese subjects in Taiwan (including 1,520 T2DM cases and 1,520 controls). The discriminative power of the prediction models with and without genotype scores was compared. We further meta-analyzed the association of these variants with T2DM by pooling all candidate-gene association studies conducted in Han Chinese.
Five risk variants in IGF2BP2 (rs4402960, rs1470579), CDKAL1 (rs10946398), SLC30A8 (rs13266634), and HHEX (rs1111875) genes were nominally associated with T2DM in our samples. The odds ratio was 2.22 (95% confidence interval, 1.81-2.73, P<0.0001) for subjects with the highest genetic score quartile (score>34) as compared with subjects with the lowest quartile (score<29). The incoporation of genotype score into the predictive model increased the C-statistics from 0.627 to 0.657 (P<0.0001). These estimates are very close to those observed in European populations. Gene-environment interaction analysis showed a significant interaction between rs13266634 in SLC30A8 gene and age on T2DM risk (P<0.0001). Further meta-analysis pooling 20 studies in Han Chinese confirmed the association of 10 genetic variants in IGF2BP2, CDKAL1, JAZF1, SCL30A8, HHEX, TCF7L2, EXT2, and FTO genes with T2DM. The effect sizes conferred by these risk variants in Han Chinese were similar to those observed in Europeans but the allele frequencies differ substantially between two populations.
We confirmed the association of 10 variants identified by European GWAS with T2DM in Han Chinese population. The incorporation of genotype scores into the prediction model led to a small but significant improvement in T2DM prediction.
几项涉及欧洲人群的全基因组关联研究（GWAS）已成功鉴定出与 2 型糖尿病（T2DM）相关的风险遗传变异。然而，这些变异在汉族人群中的作用尚未完全阐明。
我们分析了在台湾的 3040 名汉族受试者（包括 1520 名 T2DM 病例和 1520 名对照）中，24 个具有报道关联的风险遗传变异的效应。比较了包含和不包含基因型评分的预测模型的判别能力。我们通过汇总所有在汉族人群中进行的候选基因关联研究，进一步对这些变异与 T2DM 的关联进行了荟萃分析。
我们的样本中，IGF2BP2（rs4402960、rs1470579）、CDKAL1（rs10946398）、SLC30A8（rs13266634）和 HHEX（rs1111875）基因中的 5 个风险变异与 T2DM 呈名义相关。与最低四分位数（评分<29）相比，评分最高四分位数（评分>34）的受试者的比值比为 2.22（95%置信区间，1.81-2.73，P<0.0001）。将基因型评分纳入预测模型可使 C 统计量从 0.627 增加到 0.657（P<0.0001）。这些估计值与欧洲人群中观察到的值非常接近。基因-环境相互作用分析显示，SLC30A8 基因中的 rs13266634 与年龄对 T2DM 风险的相互作用非常显著（P<0.0001）。进一步对汉族人群中 20 项研究的荟萃分析证实了 IGF2BP2、CDKAL1、JAZF1、SCL30A8、HHEX、TCF7L2、EXT2 和 FTO 基因中的 10 个遗传变异与 T2DM 的关联。这些风险变异在汉族人群中赋予的效应大小与在欧洲人群中观察到的相似，但两个人群的等位基因频率差异很大。
我们证实了欧洲 GWAS 鉴定的 10 个变异与汉族人群的 T2DM 相关。将基因型评分纳入预测模型可使 T2DM 预测略有但显著改善。
