Identification of multiple novel susceptibility genes associated with autoimmune thyroid disease

作者：Xueying Liu, Yahu Miao, Chao Liu, Lu Wan, Qing Feng, Qiu Zhang · 发表于：Frontiers in Immunology · 年份：2023 · DOI：10.3389/fimmu.2023.1161311 · 被引用次数：17 · 研究领域：Genetic Associations and Epidemiology、Thyroid Disorders and Treatments、Diabetes and associated disorders

Background Autoimmune thyroid disease (AITD) is induced by various factors, including inheritability, which regulates gene expression. Multiple loci correlated with AITD have been discovered utilizing genome-wide association studies (GWASs). Nevertheless, demonstrating the biological relevance and function of these genetic loci is difficult. Methods The FUSION software was utilized to define genes that were expressed differentially in AITD using a transcriptome-wide association study (TWAS) method in accordance with GWAS summary statistics from the largest genome-wide association study of 755,406 AITD individuals (30,234 cases and 725,172 controls) and levels of gene expression from two tissue datasets (blood and thyroid). Further analyses were performed such as colocalization, conditional, and fine-mapping analyses to extensively characterize the identified associations, using functional mapping and annotation (FUMA) to conduct functional annotation of the summary statistics of 23329 significant risk SNPs ( P < 5 × 10 −8 ) recognized by GWAS, together with summary-data-based mendelian randomization (SMR) for identifying functionally related genes at the loci in GWAS. Results There were 330 genes with transcriptome-wide significant differences between cases and controls, and the majority of these genes were new. 9 of the 94 unique significant genes had strong, colocalized, and potentially causal correlations with AITD. Such strong associations included CD247 , TPO , KI...