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)是一种慢性疾病，其特征是与高度残疾和低生活质量相关的活动水平大幅减少或损害。据估计，英国有25万人受到影响，他们经常因为误解而面临耻辱。尽管它给患者、经济和NHS带来了高昂的成本，但我们对ME/CFS的原因以及如何有效治疗的了解比我们对许多更罕见、更少致残性疾病的了解更少。来自小型研究的ME/CFS研究结果往往没有得到其他研究人员的证实，这对这种情况没有帮助。我们的项目试图揭示一个人的DNA(包括他们的基因)中的差异，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，所以要找到它们，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的主要优势是它是不偏不倚的，因此它是发现疾病遗传原因和新生物学的理想选择。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、生物学途径和细胞类型。通过这种方式，我们打算产生强有力的科学线索，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将导致诊断测试和有针对性的治疗的发展。利用与患者和公众参与(PPI)开发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-每个人都被临床诊断为ME/CFS，并符合广泛使用的加拿大共识或IOM/NAM标准。一个系统将让研究人员轻松获得这一队列的DNA数据、问卷答案和其他信息，使他们能够设计更好、更便宜的实验。这些数据将被适当地匿名，并安全可靠地保存。我们的经验是，大多数患者同意就参与未来研究的事宜再次联系。这将使研究人员更容易提供高质量的研究。研究伙伴关系将研究机构与患有自我保护的人及其照顾者联系起来。我们的PPI团队包括Forward-ME(涵盖10个英国ME/CFS慈善机构)和Science for ME的代表。这项提案是由整个伙伴关系中的每个人根据NIHR的国家公众参与标准发起、计划和编写的。

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.