Common genetic factors among autoimmune diseases

• 成果类型: Review
• 署名作者: Harroud, Adil; Hafler, David A.
• 署名单位: McGill University; McGill University; McGill University; Yale University; Yale University; Harvard University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8441
• DOI: 10.1126/science.adg2992
• 发表日期: 2023-05-05
• 页码: 485-490
• 关键词: causal variants; risk variants; susceptibility; associations

摘要

Autoimmune diseases display a high degree of comorbidity within individuals and families, suggesting shared risk factors. Over the past 15 years, genome-wide association studies have established the polygenic basis of these common conditions and revealed widespread sharing of genetic effects, indicative of a shared immunopathology. Despite ongoing challenges in determining the precise genes and molecular consequences of these risk variants, functional experiments and integration with multimodal genomic data are providing valuable insights into key immune cells and pathways driving these diseases, with potential therapeutic implications. Moreover, genetic studies of ancient populations are shedding light on the contribution of pathogen-driven selection pressures to the increased prevalence of autoimmune disease. This Review summarizes the current understanding of autoimmune disease genetics, including shared effects, mechanisms, and evolutionary origins.