JDRF/Wellcome Diabetes and Inflammation Laboratory, Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
Nat Immunol. 2018 Jul;19(7):674-684. doi: 10.1038/s41590-018-0129-8. Epub 2018 Jun 20.
Genome-wide association studies are transformative in revealing the polygenetic basis of common diseases, with autoimmune diseases leading the charge. Although the field is just over 10 years old, advances in understanding the underlying mechanistic pathways of these conditions, which result from a dense multifactorial blend of genetic, developmental and environmental factors, have already been informative, including insights into therapeutic possibilities. Nevertheless, the challenge of identifying the actual causal genes and pathways and their biological effects on altering disease risk remains for many identified susceptibility regions. It is this fundamental knowledge that will underpin the revolution in patient stratification, the discovery of therapeutic targets and clinical trial design in the next 20 years. Here we outline recent advances in analytical and phenotyping approaches and the emergence of large cohorts with standardized gene-expression data and other phenotypic data that are fueling a bounty of discovery and improved understanding of human physiology.
全基因组关联研究在揭示常见疾病的多基因基础方面具有变革性，自身免疫性疾病更是引领了这一研究。尽管该领域只有 10 多年的历史，但在理解这些疾病的潜在机制途径方面已经取得了进展，这些疾病是由遗传、发育和环境因素密集的多因素混合引起的，包括对治疗可能性的深入了解。然而，对于许多已确定的易感区域，确定实际的因果基因和途径及其对改变疾病风险的生物学影响仍然是一个挑战。正是这种基础知识将为未来 20 年的患者分层、治疗靶点的发现和临床试验设计的革命提供支撑。在这里，我们概述了分析和表型方法的最新进展，以及出现了具有标准化基因表达数据和其他表型数据的大型队列，这推动了大量的发现，并提高了对人类生理学的理解。
