A Genetic Predictive Model Estimating the Risk of Developing Adolescent Idiopathic Scoliosis
A Genetic Predictive Model Estimating the Risk of Developing Adolescent Idiopathic Scoliosis
复制标题
评估青少年特发性脊柱侧凸风险的遗传预测模型
DOI：
10.2174/1389202920666190730132411
复制
发表时间：
2019-05
期刊：
影响因子：
2.6
通讯作者：
Zezhang Zhu
中科院分区：
文献类型：
--
作者：
Leilei Xu;Zhichong Wu;Chao Xia;Nelson Tang;Jack C.Y.Cheng;Yong Qiu;Zezhang Zhu
背景：以往的GWAS已发现与青少年特发性脊柱侧凸(AIS)相关的几种易感变异。基于这些变异的风险预测可能会改善疾病的预后。我们的目的是评估遗传因素在AIS发病中的综合作用，并进一步开发遗传预测模型。方法：914例AIS患者和1441例正常对照进入发现阶段，871例AIS患者和1239例正常对照进入复制阶段。对LBX1的rs678741、AJAP1的rs241215、PAX3的rs13398147、BNC2的rs16934784、GPR126的rs2050157、PAX1的rs2180439、bcl2的rs4940576、Meis1的rs7593846、MAGI1的rs7633294和tnik的rs9810566进行了基因分型。采用Logistic回归分析建立风险预测模型。在复制阶段为每个参与者计算预测的风险分数。结果：成功验证了这10个变异与AIS的关联。所建立的模型可以解释约7.9%的总体差异。在复制阶段，患者的风险评分显著高于对照组(44.2vs.33.9±12.5p<；0.001)。患者的风险评分，即40分的比例明显高于对照组(59%比28.9%，p<；0.001)。结论：基于已报道的遗传变异的风险预测模型具有显著的区分力。需要更多的临床和遗传因素的研究，以进一步提高预测AIS发病的可能性。
Background: Previous GWASs have revealed several susceptible variants associated with adolescent idiopathic scoliosis (AIS). Risk prediction based on these variants can potentially improve disease prognosis. We aimed to evaluate the combined effects of genetic factors on the development of AIS and to further develop a genetic predictive model. Methods: A total of 914 AIS patients and 1441 normal controls were included in the discovery stage, which was followed by the replication stage composed of 871 patients and 1239 controls. Genotyping assay was performed to analyze 10 previously reported susceptible variants, including rs678741 of LBX1, rs241215 of AJAP1, rs13398147 of PAX3, rs16934784 of BNC2, rs2050157 of GPR126, rs2180439 of PAX1, rs4940576 of BCL2, rs7593846 of MEIS1, rs7633294 of MAGI1 and rs9810566 of TNIK. Logistic regression analysis was performed to generate a risk predictive model. The predicted risk score was calculated for each participant in the replication stage. Results: The association of the 10 variants with AIS was successfully validated. The established model could explain approximately 7.9% of the overall variance. In the replication stage, patients were found to have a remarkably higher risk score as compared to the controls (44.2 ± 14.4 vs. 33.9 ± 12.5, p <0.001). There was a remarkably higher proportion of the risk score i.e. >40 in the patients than in the controls (59% vs. 28.9%, p <0.001). Conclusion: Risk predictive model based on the previously reported genetic variants has a remarkable discriminative power. More clinical and genetic factors need to be studied, to further improve the proba-bility to predict the onset of AIS.
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BNC2基因的遗传变异与中国人群青少年特发性脊柱侧弯存在功能相关性
影响因子：
3.1
作者：
Xu Leilei;Xia Chao;Qin Xiaodong;Sun Weixiang;Tang Nelson Leung-Sang;Qiu Yong;Cheng Jack Chun-Yiu;Zhu Zezhang
通讯作者：
Zhu Zezhang
影响因子：
3
作者：
Miller, NH;Justice, CM;Wilson, AF
通讯作者：
Wilson, AF
影响因子：
3
作者：
Xu, Leilei;Qin, Xiaodong;Zhu, Zezhang
通讯作者：
Zhu, Zezhang
影响因子：
2.8
作者：
Xu, Leilei;Qiu, Xusheng;Qiu, Yong
通讯作者：
Qiu, Yong
DOI：
10.1534/g3.114.015669
发表时间：
2014-12-12
期刊：
G3 (Bethesda, Md.)
影响因子：
--
作者：
Baschal EE;Wethey CI;Swindle K;Baschal RM;Gowan K;Tang NL;Alvarado DM;Haller GE;Dobbs MB;Taylor MR;Gurnett CA;Jones KL;Miller NH
通讯作者：
Miller NH