精神分裂症数据的统计方法研究

Schizophrenia, as one of the common complex human disease, is developed by genetic and environmental factors, whose pathopoiesis has not been clear so far. Therefore, it is a significant issue for recent medical studies to treat schizophrenia on a level of gene and environmental factors. Haplotype-based association methods，which are used in gene mapping, provide great power and efficiency in the discovery and characterization of the genetic basis of complex human diseases. However, when investigating many SNP loci, the large number of haplotypes limits the power and efficiency of the methods; simultaneously, the great number of environmental variables suffers from the similar problems, caused by the number of parameters. Hence, we focus on the research on the associations between schizophrenia and genetic and environmental factors in this project. Haplotype clustering, and model selection to the environmental factors could offer appealing solutions respectively. And we introduce a two-stage strategy together with conditional model, to investigate genetic and environmental factors simultaneously, including their interactions. Furthermore, we will deliberate the relationship between different types of schizophrenia and the genetic and environmental factors. Finally, we will provide our softwares to genetic epidemiology researchers in order to generalize our project.

精神分裂症属于人类常见复杂疾病，其发生涉及遗传和环境因素的共同作用，且致病机制至今仍未被阐明，因此，在基因水平与外界环境因素上预防和治疗精神分裂症是当前医学研究中的重大课题。基于单倍型的关联分析方法是基因定位研究的一类统计方法，而且在发现与刻画人类复杂疾病的遗传基础时拥有很高的功效。然而，当研究的SNP位点很多时，迅速增加的单倍型种类限制了方法的效率、功效等；同时，大量的环境变量也带来同样的问题。因此，在本项目中，我们重点开展精神分裂症与遗传因素和环境因素的关联性的研究，对单倍型进行聚类，对环境变量进行模型选择，并基于"分而治之"的思想，利用两阶段法同时考察遗传因素和环境因素及其交互。进一步，研究精神分裂症各个分型与遗传因素和环境因素的关系，给流行病实际工作者提供理论上的指导和应用上的便利。

本项目旨在利用统计方法，研究和探讨精神分裂症在基因与环境水平上的危险因素，并将方法推广到其他慢性病的研究中去。经过三年的努力，我们对精神分裂症及其他慢性病进行了深入的研究，并取得了预期的成果。.首先，我们提出的一个基于U-统计量的非参数方法，探索内化性精神障碍数据，论文 “Nonparametric tests of associations with diseases based on U-statistics”于2014年发表在Annals of Human Genetics（SCI，IF 2.211）上。.其次，与精神分裂症类似，其他慢性病的危险因素都不是单独存在的，所以，我们从危险因素聚集的角度研究疾病，论文“Risk Factors for Cardiovascular Disease and Their Clustering among Adults in Jilin (China)”于2015年底发表在International Journal of Environmental Research and Public Health（SCI，IF 2.063）上。.随后，我们发现肥胖不但是精神分裂症，也是其他慢性病的重要影响因素，因此，我们试图从肥胖的角度研究慢性病，论文“Optimal cut-off of obesity indices to predict cardiovascular diseases risk factors and metabolic syndrome among adults in Northeast China”与“Comparison of the Combined Obesity Indices to Predict Cardiovascular Diseases Risk Factors and Metabolic Syndrome in Northeast China”于2016年分别发表在BMC Public Health（SCI，IF 2.209）与International Journal of Environmental Research and Public Health（SCI，IF 2.035）上。.以上是本项目的主要成果，此外还有一篇发表的中文核心论文和两篇慢性病研究的草稿正在修改与投稿。