Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Big Data Institute, University of Oxford, Oxford, UK.
Nat Rev Genet. 2021 Mar;22(3):137-153. doi: 10.1038/s41576-020-00297-6. Epub 2020 Dec 4.
Understanding how human genetics influence infectious disease susceptibility offers the opportunity for new insights into pathogenesis, potential drug targets, risk stratification, response to therapy and vaccination. As new infectious diseases continue to emerge, together with growing levels of antimicrobial resistance and an increasing awareness of substantial differences between populations in genetic associations, the need for such work is expanding. In this Review, we illustrate how our understanding of the host-pathogen relationship is advancing through holistic approaches, describing current strategies to investigate the role of host genetic variation in established and emerging infections, including COVID-19, the need for wider application to diverse global populations mirroring the burden of disease, the impact of pathogen and vector genetic diversity and a broad array of immune and inflammation phenotypes that can be mapped as traits in health and disease. Insights from study of inborn errors of immunity and multi-omics profiling together with developments in analytical methods are further advancing our knowledge of this important area.
了解人类遗传学如何影响传染病易感性,为深入了解发病机制、潜在药物靶点、风险分层、治疗反应和疫苗接种提供了机会。随着新的传染病不断出现,以及抗生素耐药性水平的不断提高,以及人们越来越意识到人群在遗传关联方面存在着实质性差异,对这类工作的需求正在不断扩大。在这篇综述中,我们通过整体方法说明了我们对宿主-病原体关系的理解是如何取得进展的,描述了当前研究宿主遗传变异在既定和新兴感染(包括 COVID-19)中的作用的策略,包括更广泛地应用于反映疾病负担的多样化全球人群的必要性,病原体和媒介遗传多样性的影响,以及可以作为健康和疾病特征进行映射的广泛的免疫和炎症表型。对先天性免疫缺陷和多组学分析的研究以及分析方法的发展,进一步推动了我们对这一重要领域的认识。