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风湿病学的遗传学革命:大规模基因组芯片和遗传图谱。

The genetics revolution in rheumatology: large scale genomic arrays and genetic mapping.

机构信息

Arthritis Research UK Centre for Genetics and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK.

NIHR Manchester Musculoskeletal Biomedical Research Unit, Manchester Academic Health Sciences Centre, Central Manchester Foundation Trust, Grafton Street. Manchester M13 9NT, UK.

出版信息

Nat Rev Rheumatol. 2017 Jul;13(7):421-432. doi: 10.1038/nrrheum.2017.80. Epub 2017 Jun 1.

Abstract

Susceptibility to rheumatic diseases, such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, juvenile idiopathic arthritis and psoriatic arthritis, includes a large genetic component. Understanding how an individual's genetic background influences disease onset and outcome can lead to a better understanding of disease biology, improved diagnosis and treatment, and, ultimately, to disease prevention or cure. The past decade has seen great progress in the identification of genetic variants that influence the risk of rheumatic diseases. The challenging task of unravelling the function of these variants is ongoing. In this Review, the major insights from genetic studies, gained from advances in technology, bioinformatics and study design, are discussed in the context of rheumatic disease. In addition, pivotal genetic studies in the main rheumatic diseases are highlighted, with insights into how these studies have changed the way we view these conditions in terms of disease overlap, pathways of disease and potential new therapeutic targets. Finally, the limitations of genetic studies, gaps in our knowledge and ways in which current genetic knowledge can be fully translated into clinical benefit are examined.

摘要

易患风湿性疾病(如骨关节炎、类风湿关节炎、强直性脊柱炎、系统性红斑狼疮、幼年特发性关节炎和银屑病关节炎)的倾向受遗传因素的影响较大。了解个体的遗传背景如何影响疾病的发生和转归,可以帮助我们更好地理解疾病的生物学机制,改善诊断和治疗方法,并最终实现疾病的预防或治愈。过去十年,在鉴定影响风湿性疾病风险的遗传变异方面取得了重大进展。目前,解析这些变异功能的艰巨任务仍在进行中。在这篇综述中,我们将结合风湿性疾病,讨论技术、生物信息学和研究设计方面的进步为遗传研究带来的主要见解。此外,我们还重点介绍了主要风湿性疾病中的关键性遗传研究,阐述了这些研究如何改变我们对这些疾病在疾病重叠、疾病途径和潜在新治疗靶点方面的认识。最后,我们还探讨了遗传研究的局限性、知识空白以及如何将当前的遗传知识充分转化为临床获益。

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