Alamad Bana, Elliott Kate, Knight Julian C
Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Chinese Academy of Medical Science Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Camb Prism Precis Med. 2024 Jan 31;2:e3. doi: 10.1017/pcm.2023.25. eCollection 2024.
The interplay between genetic and environmental factors plays a significant role in interindividual variation in immune and inflammatory responses. The availability of high-throughput low-cost genotyping and next-generation sequencing has revolutionized our ability to identify human genetic variation and understand how this varies within and between populations, and the relationship with disease. In this review, we explore the potential of genomics for patient benefit, specifically in the diagnosis, prognosis and treatment of inflammatory and immune-related diseases. We summarize the knowledge arising from genetic and functional genomic approaches, and the opportunity for personalized medicine. The review covers applications in infectious diseases, rare immunodeficiencies and autoimmune diseases, illustrating advances in diagnosis and understanding risk including use of polygenic risk scores. We further explore the application for patient stratification and drug target prioritization. The review highlights a key challenge to the field arising from the lack of sufficient representation of genetically diverse populations in genomic studies. This currently limits the clinical utility of genetic-based diagnostic and risk-based applications in non-Caucasian populations. We highlight current genome projects, initiatives and biobanks from diverse populations and how this is being used to improve healthcare globally by improving our understanding of genetic susceptibility to diseases and regional pathogens such as malaria and tuberculosis. Future directions and opportunities for personalized medicine and wider application of genomics in health care are described, for the benefit of individual patients and populations worldwide.
遗传因素与环境因素之间的相互作用在个体免疫和炎症反应的差异中起着重要作用。高通量低成本基因分型和新一代测序技术的出现，彻底改变了我们识别人类基因变异、理解其在人群内部和人群之间的差异以及与疾病关系的能力。在本综述中，我们探讨了基因组学为患者带来益处的潜力，特别是在炎症和免疫相关疾病的诊断、预后和治疗方面。我们总结了从遗传和功能基因组学方法中获得的知识，以及个性化医疗的机遇。本综述涵盖了在传染病、罕见免疫缺陷和自身免疫性疾病中的应用，阐述了诊断方面的进展以及对风险的理解，包括多基因风险评分的使用。我们进一步探讨了其在患者分层和药物靶点优先级确定方面的应用。本综述强调了该领域面临的一个关键挑战，即基因组研究中缺乏足够的遗传多样性人群代表性。这目前限制了基于基因的诊断和基于风险的应用在非白种人群中的临床效用。我们重点介绍了来自不同人群的当前基因组项目、倡议和生物样本库，以及它们如何通过增进我们对疾病和疟疾、结核病等地区病原体的遗传易感性的理解，来改善全球医疗保健。本文还描述了个性化医疗的未来方向和机遇，以及基因组学在医疗保健中更广泛应用的前景，以造福全球的个体患者和人群。
