Science and technology field: This project belongs to the field of pathogenesis, diagnosis and treatment of autoimmune thyroid diseases (AITDs). At present, the pathogenesis of AITDs is not clear. We conducted in-depth research from the perspective of genetics and epigenetics to further clarify the pathogenesis of AITDs. Main technological innovation contents: This project has gone through 12 years of research, and the main contents and innovative results obtained are as follows: 1. The relationship between single nucleotide polymorphisms in two thyroid autoantigen genes and multiple immune-related genes and the incidence of AITDs was tested, and thyroglobulin was discovered Thyroglobulin (Tg) gene and TSH receptor (TSHR) gene are susceptible genes to AITDs in Han population in China; The following 24 immune-related genes were found: CD40, CTLA-4, IL-17, IL-21, IL-21R, ST2, IL18R1, IL18RAP, CLEC16A, TNFAIP3, STAT4, IRAK1, MECP2, TRAF1, RNSET2, UBE2L3, VDR, TNFRSF1A, IKZF3, IRGM, BANK1, TNFSF4, STAT3 and IL-22 can increase the risk of AITDs. Most of the research results of this project are reported for the first time at home and abroad. They are original research and are highly innovative and advanced. 2. A systematic and specific differential copy number variation (CNV) expression profile of Graves rsquo;disease (GD) was initially established. Subsequently, some differentially expressed CNV genes screened by the chip were verified, and two SNP loci related to the differentially expressed CNV gene TRI6 were detected. The results showed that the copy numbers of CFH, CFHR1, KIA0125, UGT2B15, UGT2B17, TRI6, and CCL3L1 were not related to the risk of GD. 3. An animal model with the main characteristics of human GD was successfully prepared by immunizing inbred BALB/c mice with an adenovirus vector expressing the A subunit of human TSH receptor (TSHR). 4. It was found for the first time that local injection of the CTLA4Ig gene in the thyroid can treat autoimmune thyroiditis by inducing the shift of Thl dominance to Th2. 5. For the first time, abnormally expressed microRNAs were found in thyroid tissue of AITDs; abnormal expression of DNA methylation and histone acetylation in peripheral blood mononuclear cells was associated with the pathogenesis of GD. Intellectual property rights and application promotion: This project is funded by three National Natural Science Foundations (30871185, 81070627, 81270871). This research resulted in 20 main papers, of which 19 were included in SCI, with a total of 284 citations. At the same time, he also participated in many academic exchanges, including oral or written exchanges and awards at the National and Shanghai Endocrinology Annual Meetings; a total of more than 40 master's and doctoral students have been trained. This research results are mainly promoted and applied in the research and clinical fields of thyroid diseases. They will help deepen endocrinologists 'understanding and understanding of the mechanism of AITDs, provide basis and ideas for precise treatment and specific immunotherapy of AITDs, and have good clinical application prospects.