A genome-wide association study of myalgic encephalomyelitis / chronic fatigue syndrome(ME/CFS)

肌痛性脑脊髓炎/慢性疲劳综合征（ME/CFS）的全基因组关联研究

• 批准号: MC_PC_20005
• 负责人: Chris Ponting
• 金额: $ 416.75万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MC_PC_20005
• 关键词: genome; wide; association; study; myalgic

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic disease characterised by substantial reduction or impairment of activity levels associated with high levels of disability and poor quality of life. It affects an estimated 250,000 people in the UK who often face stigma because of misconceptions. Despite its high cost to patients, the economy and the NHS, we know less about the causes of ME/CFS and how to treat it effectively than we do about many rarer and less disabling diseases. This situation is not helped by ME/CFS research findings from small studies often not being confirmed by other researchers. Our project seeks to reveal differences in a person’s DNA (including their genes) that alter their risk of developing ME/CFS. These changes in risk are typically small and so to find them we need to study a large number – at least 20,000 – of people with ME.We propose using a genome-wide association study (GWAS) design because it has already helped uncover the biological roots of many other complex diseases. GWAS’s major strength is that it is unbiased, so it is ideal for discovering genetic causes of disease and new biology. Next, we will find out whether the genetics of ME/CFS overlaps with other diseases. Then we will predict genes, biological pathways and cell-types directly implicated in ME/CFS. In this way we intend to generate strong scientific leads that researchers can pursue with new experiments. We hope this work will ultimately lead to the development of diagnostic tests and targeted treatments.Using orchestrated marketing and PR campaigns developed with Patient and Public Involvement (PPI), we will build a research cohort of 20,000 people – each clinically diagnosed with ME/CFS and who meet the widely-used Canadian Consensus or IOM/NAM criteria. A system will give researchers easy access to this cohort’s DNA data, questionnaire answers and other information, to allow them to design better and cheaper experiments. The data will be appropriately anonymised and held safely and securely.Our experience is that most patients consent to be re-contacted about taking part in future studies. This will make it easier for researchers to deliver high quality studies. The Research Partnership links research institutions with people with ME and their carers. Our PPI team includes representatives from Forward-ME (covering ten UK ME/CFS charities) and Science for ME. This proposal was initiated, planned and written by everyone across this Partnership in accordance with the NIHR’s National Standards for Public Involvement.

肌痛性脑脊髓炎/慢性疲劳综合症（ME/CFS）是一种慢性疾病，其特征是活动水平大幅降低或受损，并伴有高度残疾和生活质量差。它影响了大约 250,000 名英国人，他们经常因误解而面临耻辱。尽管 ME/CFS 给患者、经济和 NHS 带来高昂的成本，但我们对 ME/CFS 的病因以及如何有效治疗它的了解还不如对许多罕见和不太致残的疾病的了解。 ME/CFS 小型研究的研究结果往往未经其他研究人员证实，对这种情况无济于事。我们的项目旨在揭示一个人 DNA（包括基因）的差异，这些差异会改变他们患 ME/CFS 的风险。这些风险变化通常很小，因此为了找到它们，我们需要研究大量（至少 20,000 名）ME 患者。我们建议使用全基因组关联研究 (GWAS) 设计，因为它已经帮助揭示了许多其他复杂疾病的生物学根源。 GWAS 的主要优势在于它不带偏见，因此非常适合发现疾病的遗传原因和新生物学。接下来，我们将找出ME/CFS的遗传学是否与其他疾病重叠。然后我们将预测与 ME/CFS 直接相关的基因、生物途径和细胞类型。通过这种方式，我们打算产生强大的科学线索，研究人员可以通过新的实验来追求。我们希望这项工作最终能够推动诊断测试和针对性治疗的发展。通过与患者和公众参与 (PPI) 共同开展的精心策划的营销和公关活动，我们将建立一个由 20,000 人组成的研究队列——每个人都经过临床诊断患有 ME/CFS，并且符合广泛使用的加拿大共识或 IOM/NAM 标准。一个系统将使研究人员能够轻松访问该群体的 DNA 数据、问卷答案和其他信息，从而使他们能够设计更好、更便宜的实验。这些数据将被适当匿名并安全可靠地保存。我们的经验是，大多数患者同意重新联系以参与未来的研究。这将使研究人员更容易提供高质量的研究。研究合作伙伴关系将研究机构与 ME 患者及其护理人员联系起来。我们的 PPI 团队包括来自 Forward-ME（涵盖十个英国 ME/CFS 慈善机构）和 Science for ME 的代表。该提案由该伙伴关系中的每个人根据 NIHR 的公众参与国家标准发起、策划和撰写。

项目成果

The genetics of ME: A commentary on Hajdarevic et al.

ME 的遗传学：Hajdarevic 等人的评论。

• DOI: 10.1016/j.bbi.2022.06.008
• 发表时间: 2022
• 期刊: Brain, behavior, and immunity
• 作者: Ponting CP

Genetic risk factors of ME/CFS: a critical review.

• DOI: 10.1093/hmg/ddaa169
• 发表时间: 2020-09-30
• 期刊: Human molecular genetics
• 影响因子: 3.5
• 作者: Dibble JJ;McGrath SJ;Ponting CP
• 通讯作者: Ponting CP

DecodeME: community recruitment for a large genetics study of myalgic encephalomyelitis / chronic fatigue syndrome.

• DOI: 10.1186/s12883-022-02763-6
• 发表时间: 2022-07-19
• 期刊: BMC NEUROLOGY
• 影响因子: 2.6
• 作者: Devereux-Cooke, Andy;Leary, Sian;McGrath, Simon J.;Northwood, Emma;Redshaw, Anna;Shepherd, Charles;Stacey, Pippa;Tripp, Claire;Wilson, Jim;Mar, Margaret;Boobyer, Danielle;Bromiley, Sam;Chowdhury, Sonya;Dransfield, Claire;Almas, Mohammed;Almelid, Oyvind;Buchanan, David;Garcia, Diana;Ireland, John;Kerr, Shona M.;Lewis, Isabel;McDowall, Ewan;Migdal, Malgorzata;Murray, Phil;Perry, David;Ponting, Chris P.;Vitart, Veronique;Wolfe, Jareth C.
• 通讯作者: Wolfe, Jareth C.