密切接触者发展为潜伏结核感染中维生素D作用的因果推断研究

对潜伏结核感染高危人群进行预防性干预，是终止结核策略研究关注的热点问题。结核患者密切接触者发展为潜伏结核感染的风险更高，免疫调节因子VitD水平与结核感染存在关联，但其作用的效应受环境、基因多态性等诸多因素间的混杂效应与交互效应影响，迫切需要崭新的方法学应用研究。.研究拟建立乌鲁木齐市结核密切接触者自然人群队列，随访观察其发生潜伏感染至结核的疾病进程，分析VitD、VitD受体及Toll样受体基因多态性与潜伏结核感染的关联性。环境-基因、基因-基因交互与混杂作用使数据呈现非线性、高维性与动态性，结合数据挖掘技术与因果推断方法，筛选关键特征因素，多因子降维法揭示环境与基因间的交互效应，倾向性评分与孟德尔随机化法控制VitD相关的混杂效应，构建贝叶斯网络推断VitD与潜伏感染结局间的因果效应与作用机制。研究可为精准确定潜伏感染目标人群，关口前移开展VitD预防性治疗提供方法学参考与证据支持。

Preventive intervention of people at high risk of latent tuberculosis infection has become a hotspot on the study of strategies to end tuberculosis. People with close contact with tubercular patients have a higher risk of developing latent tuberculosis infection. The level of immunoregulatory factor vitamin D is associated with tuberculosis infection susceptibility, but those are affected by confounding and interactive effects among many factors such as environment and genetic polymorphism. Therefore, there is an urgent need for new methodological application research..The research plans to establish a natural population cohort of close contacts of tuberculosis in Urumqi, follow up to observe the disease progression from close contacts to latent infection and tuberculosis patient, and analyze the complex association between vitamin D, vitamin D receptor and Toll-like receptor gene polymorphisms and latent tuberculosis infection. The interaction and confounding effects between environment and gene, gene and gene make the data non-linear, high-dimensional and dynamic. It is new ideas of combining data mining techniques and causal inference methods to analyze data information, and screen out the key characteristic factors. The multifactor dimensionality reduction method are applied to reveal environment and genes interaction effect, propensity score and Mendelian randomization method to control the confounding effects related to vitamin D, and Bayesian network models are constructed to infer the causal effect and mechanism between vitamin D and the outcome of latent infection. The research can provide methodological reference and evidence support for accurately identifying the target population of latent tuberculosis infection and moving forward to carry out vitamin D preventive treatment for tuberculosis disease.