免疫介导肾小球疾病是我国尿毒症的主要病因，系统全面地探讨该类疾病的共性和个性遗传学机制，是发现和揭示新的致病分子和/或途径及其致病机制，构建新型分子诊疗体系，最终提高我国肾脏病诊疗水平的关键和当务之急。本项目以IgA肾病（器官特异性疾病）、狼疮性肾炎（系统性疾病）以及兼备两者共同特点的紫癜性肾炎为切入点，深度分析和优化前期已经完成的全基因组关联分析（GWAS）数据，通过虚拟估算、基因群分析和生物信息学分析，以及独立人群验证和疾病亚表型分析，探讨共性和特性相关基因及基因涉及通路遗传变异与疾病表型的相关性；利用病人血液、尿液、肾活检组织和体外（细胞、动物）模型，探讨相关基因及其表达和调控在临床表型、细胞表型中的作用，确立表型发生的分子途径，明确基于遗传背景的循环免疫和肾脏局部免疫机制，进一步明确不同免疫介导肾小球疾病免疫机制与肾脏受累的致病机制，为优化个体化诊疗靶标提供线索和实验证据。

IgA nephropathy (IgAN), lupus nephritis (LN) and Henoch-Schonlein purpura nephritis (HSPN) are major types of immune-mediated glomerular diseases (GN) with high prevalence in Chinese population, leading to end-stage renal disease (ESRD), which means the requirement of renal replacement therapy (RRT), itself associated with high cost and unacceptable levels of mortality. Current diagnosis and treatment is mainly based on clinical symptoms and histological description, which do not necessarily reflect underlying pathophysiology or provide information on prognosis. With the advanced new technologies, evolution towards personalized medicine is urgently needed. Recent genetic studies have revealed highly shared immunological mechanisms in immune-related disorders. On the path from systems genetics to systems biology, we aim to analyze the shared and disease-specific genetic variants associated with them, in order to identify potential causal variants and explore the downstream associated pathways to be potentially targeted with disease-specific and patient-specific therapies.