Lam Hoang V, Nguyen Dat T, Nguyen Cao D
Department of Endocrinology, Cho Ray Hospital, Ho Chi Minh City, Vietnam.
Department of Science and Technology, Hoa Sen University, Ho Chi Minh City, Vietnam.
PLoS One. 2017 May 16;12(5):e0176341. doi: 10.1371/journal.pone.0176341. eCollection 2017.
We presented a risk assessment model to distinguish between type 1 diabetes (T1D) affected and unaffected siblings using only three single nucleotide polymorphism (SNP) genotypes. In addition we calculated the heritability from genome-wide identity-by-descent (IBD) sharing between full siblings. We analyzed 1,253 pairs of affected individuals and their unaffected siblings (750 pairs from a discovery set and 503 pairs from a validation set) from the T1D Genetics Consortium (T1DGC), applying a logistic regression to analyze the area under the receiver operator characteristic (ROC) curve (AUC). To calculate the heritability of T1D we used the Haseman-Elston regression analysis of the squared difference between the phenotypes of the pairs of siblings on the estimate of their genome-wide IBD proportion. The model with only 3 SNPs achieving an AUC of 0.75 in both datasets outperformed the model using the presence of the high-risk DR3/4 HLA genotype, namely AUC of 0.60. The heritability on the liability scale of T1D was approximately from 0.53 to 0.92, close to the results obtained from twin studies, ranging from 0.4 to 0.88.
我们提出了一种风险评估模型，仅使用三种单核苷酸多态性（SNP）基因型来区分1型糖尿病（T1D）患者和未患病的兄弟姐妹。此外，我们根据全同胞之间全基因组同源性（IBD）共享情况计算了遗传力。我们分析了来自T1D遗传联盟（T1DGC）的1253对患病个体及其未患病的兄弟姐妹（750对来自发现集，503对来自验证集），应用逻辑回归分析受试者工作特征（ROC）曲线下面积（AUC）。为了计算T1D的遗传力，我们使用Haseman-Elston回归分析，根据兄弟姐妹对的全基因组IBD比例估计值，分析其表型之间平方差。仅包含3个SNP的模型在两个数据集中的AUC均达到0.75，优于使用高风险DR3/4 HLA基因型存在情况的模型，后者的AUC为0.60。T1D易患性尺度上的遗传力约为0.53至0.92，与双胞胎研究得到的结果相近，范围为0.4至0.88。
