Cumulative Evidence on Associations between Genetic Variants and Autoimmune Hepatitis  

作　　者：Dongqing Gu Yizhou Wang Liang Ge Min Zhang Dongqing Gu;Yizhou Wang;Liang Ge;Min Zhang(Department of Obstetrics and Gynecology, Chongqing Health Center for Women and Children, Women and Children’s Hospital of Chongqing Medical University, Chongqing, China;Department of Pathology, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, China;Laboratory of Infection and Immunity, West China School of Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, China;Clinical and Public Health Research Center, Women and Children’s Hospital of Chongqing Medical University, Chongqing, China)

机构地区：[1]Department of Obstetrics and Gynecology, Chongqing Health Center for Women and Children, Women and Children’s Hospital of Chongqing Medical University, Chongqing, China [2]Department of Pathology, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, China [3]Laboratory of Infection and Immunity, West China School of Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, China [4]Clinical and Public Health Research Center, Women and Children’s Hospital of Chongqing Medical University, Chongqing, China

出　　处：《Journal of Biosciences and Medicines》2024年第12期560-571,共12页生物科学与医学(英文)

摘　　要：Genetic factors play a critical role in autoimmune hepatitis (AIH), and numerous studies have been conducted to identify variants associated with the risk of AIH. However, our knowledge of these genetic risk factors is still limited. In this study, we aim to provide a comprehensive synopsis of the genetic architecture of this disease. A systematic search was conducted to identify published studies on the associations between genetic variants and the risk of AIH. Meta-analyses were conducted to calculate the pooled odds ratio (OR) and 95% confidence interval (CI). Then, the cumulative evidence was evaluated for significant associations according to the Venice criteria and false-positive report probability. Finally, functional annotations and pathway analyses were conducted to identify potential pathogenic loci and related pathways. In total, 62 studies involving 11,068 cases and 45,482 controls were included to assess the association between 75 genetic variants and the risk of AIH. Among them, 24 variants were associated with the risk of AIH, and there is strong cumulative evidence supporting these associations. Importantly, HLA DRB1*0301 (OR: 3.023, 95% CI: 2.443 - 1.678, P = 2.81 × 10?24) and DRB3*0101 (OR: 3.667, 95% CI: 2.649 - 5.075, P = 4.69 × 10?15) are newly identified genome-wide significant risk loci. In addition, the rs3184504 variant (OR: 1.305, 95% CI: 1.122 - 1.516, P = 0.001) in the SH2B3 gene is a potential functional mutation. GO pathway analysis suggests that these genes are enriched in antigen processing and presentation, response to interferon-gamma, and immune response-regulating signaling pathways. This study comprehensively summarizes the genetic architecture of AIH and provides cumulative evidence. We have identified two new loci that exceed genome-wide significance. The findings from this study will offer new insights into the pathogenesis of AIH.Genetic factors play a critical role in autoimmune hepatitis (AIH), and numerous studies have been conducted to identify variants associated with the risk of AIH. However, our knowledge of these genetic risk factors is still limited. In this study, we aim to provide a comprehensive synopsis of the genetic architecture of this disease. A systematic search was conducted to identify published studies on the associations between genetic variants and the risk of AIH. Meta-analyses were conducted to calculate the pooled odds ratio (OR) and 95% confidence interval (CI). Then, the cumulative evidence was evaluated for significant associations according to the Venice criteria and false-positive report probability. Finally, functional annotations and pathway analyses were conducted to identify potential pathogenic loci and related pathways. In total, 62 studies involving 11,068 cases and 45,482 controls were included to assess the association between 75 genetic variants and the risk of AIH. Among them, 24 variants were associated with the risk of AIH, and there is strong cumulative evidence supporting these associations. Importantly, HLA DRB1*0301 (OR: 3.023, 95% CI: 2.443 - 1.678, P = 2.81 × 10?24) and DRB3*0101 (OR: 3.667, 95% CI: 2.649 - 5.075, P = 4.69 × 10?15) are newly identified genome-wide significant risk loci. In addition, the rs3184504 variant (OR: 1.305, 95% CI: 1.122 - 1.516, P = 0.001) in the SH2B3 gene is a potential functional mutation. GO pathway analysis suggests that these genes are enriched in antigen processing and presentation, response to interferon-gamma, and immune response-regulating signaling pathways. This study comprehensively summarizes the genetic architecture of AIH and provides cumulative evidence. We have identified two new loci that exceed genome-wide significance. The findings from this study will offer new insights into the pathogenesis of AIH.

关 键 词：Autoimmune Hepatitis Genetic Architecture Cumulative Evidence Functional Annotations HLA 

分 类 号：R57[医药卫生—消化系统]