基于易感基因的麻风风险预测模型的构建及效能研究

目的：基于麻风全基因组关联研究（GWAS）发现的18个易感位点，联合流行区域及家族史信息，建立中国人群麻风风险预测模型。方法：通过SNP位点等权重风险评分(GRS)和加权遗传风险评分(wGRS)法对5792例麻风患者和8097名正常对照计算易感位点的联合效应。以不同的方式联合遗传风险评分、地域及家族史信息，构建麻风风险预测模型，并绘制受试者工作曲线来评价模型。结果：wGRS联合地域及家族史信息建立的风险预测模型最佳，其曲线下面积（AUC）为0.758（95% CI：0.750~0.766）。结论：麻风易感位点间存在显著的联合作用，加权遗传风险评分联合地域及家族史信息建立的风险预测模型，能更好地预测麻风发病风险。

Risk prediction model of leprosy based on the susceptibility genes and its power study

Objective: To evaluate the risk of leprosy by considering information on epidemic region and family history when combined with the 18 known susceptibility loci identified by genome-wide association studies (GWASs) associated with leprosy. Methods: Genetic risk score (GRS) and weighted genetic risk score( wGRS) were calculated to evaluate the joint effects of 18 susceptibility loci. Multiple models combining genetic loci and region and family history information were established. Receiver operating characteristic curve analysis was used to compare the power of different predictive models. Results:The model incorporating wGRS and information on epidemic region and family history was the best one to predict leprosy risk in Chinese popu-lation, with all area under curve of 0.758 (95% CI:0.750~0.766). Conclusion: Eighteen known suscepti-bility loci identified by GWASs jointly influence the risk of leprosy. The combination of 18 known susceptibility loci and information on epidemic region and family history can improve the performance of risk predictive mod-el for the occurrence of leprosy.