{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T01:07:12Z","timestamp":1794359232610,"version":"4.9.0"},"reference-count":47,"publisher":"National Institute for Health and Care Research","license":[{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nationalarchives.gov.uk\/doc\/open-government-licence\/version\/3\/"}],"funder":[{"DOI":"10.13039\/501100001981","name":"ME Research UK","doi-asserted-by":"crossref","award":["PhD-level research funding"],"award-info":[{"award-number":["PhD-level research funding"]}],"id":[{"id":"10.13039\/501100001981","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIHR and MRC","award":["MC_PC_20005"],"award-info":[{"award-number":["MC_PC_20005"]}]}],"content-domain":{"domain":["openresearch.nihr.ac.uk"],"crossmark-restriction":false},"short-container-title":["NIHR Open Res"],"abstract":"<ns3:p>Background Progress in Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (ME\/CFS) research is being slowed by the relatively small-scale studies being performed whose results are often not replicated. Progress could be accelerated by analyses of large population-scale projects, such as UK Biobank (UKB), which provide extensive phenotype and genotype data linked to both ME\/CFS cases and controls. Methods Here, we analysed the overlap and discordance among four UKB-defined ME\/CFS cohorts, and additional questionnaire data when available. Results A total of 5,354 UKB individuals were linked to at least one piece of evidence of MECFS, a higher proportion (1.1%) than most prevalence estimates. Only a third (36%; n=1,922) had 2 or more pieces of evidence for MECFS, in part due to data missingness. For the same UKB participant, ME\/CFS status defined by ICD-10 (International Classification of Diseases, Tenth Revision) code G93.3 (Post-viral fatigue syndrome) was most likely to be supported by another data type (72%); ME\/CFS status defined by Pain Questionnaire responses is least likely to be supported (43%), in part due to data missingness. Conclusions We conclude that ME\/CFS status in UKB, and potentially other biobanks, is best supported by multiple, and not single, lines of evidence. Finally, we raise the estimated ME\/CFS prevalence in the UK to 410,000 using the most consistent evidence for ME\/CFS status, and accounting for those who had no opportunity to participate in UKB due to being bed- or house-bound.<\/ns3:p>","DOI":"10.3310\/nihropenres.13956.1","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T05:45:09Z","timestamp":1745819109000},"page":"39","update-policy":"https:\/\/doi.org\/10.3310\/nihropenres.crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Defining a High-Quality Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome cohort in UK Biobank"],"prefix":"10.3310","volume":"5","author":[{"given":"Gemma L.","family":"Samms","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0202-7816","authenticated-orcid":false,"given":"Chris P.","family":"Ponting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"6221","published-online":{"date-parts":[[2025,4,28]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"216","DOI":"10.3390\/metabo10050216","article-title":"Letter to the editor of Metabolites.","volume":"10","author":"M Hanson","year":"2020","journal-title":"Metabolites."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"443-458","DOI":"10.1016\/j.molmed.2024.02.003","article-title":"Unravelling shared mechanisms: insights from recent ME\/CFS research to illuminate long COVID pathologies.","volume":"30","author":"S Annesley","year":"2024","journal-title":"Trends Mol Med."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"59-65","DOI":"10.1016\/s0022-3956(96)00050-7","article-title":"Precipitating factors for the Chronic Fatigue Syndrome.","volume":"31","author":"I Salit","year":"1997","journal-title":"J Psychiatr 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Syndr."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"20","DOI":"10.3310\/nihropenres.13421.4","article-title":"Typing Myalgic Encephalomyelitis by infection at onset: a decodeme study [version 4; peer review: 2 approved].","volume":"3","author":"A Bretherick","year":"2023","journal-title":"NIHR Open Res."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"83-93","DOI":"10.1080\/21641846.2022.2062169","article-title":"Updated ME\/CFS prevalence estimates reflecting post-COVID increases and associated economic costs and funding implications.","volume":"10","author":"A Mirin","year":"2022","journal-title":"Fatigue."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"200-211","DOI":"10.1080\/21641846.2022.2124775","article-title":"Research priorities for Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (ME\/CFS): the results of a James Lind alliance priority setting exercise.","volume":"10","author":"S Tyson","year":"2022","journal-title":"Fatigue."},{"key":"ref-10","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-023-02893-9","article-title":"Biomarkers for Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (ME\/CFS): a systematic review.","volume":"21","author":"R Maksoud","year":"2023","journal-title":"BMC Med."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"R117-R124","DOI":"10.1093\/hmg\/ddaa169","article-title":"Genetic risk factors of ME\/CFS: a critical review.","volume":"29","author":"J Dibble","year":"2020","journal-title":"Hum Mol Genet."},{"key":"ref-12","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-45107-3","article-title":"Deep phenotyping of post-infectious Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome.","volume":"15","author":"B Walitt","year":"2024","journal-title":"Nat Commun."},{"key":"ref-13","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-022-02763-6","article-title":"DecodeME: community recruitment for a large genetics study of Myalgic Encephalomyelitis \/ Chronic Fatigue Syndrome.","volume":"22","author":"A Devereux-Cooke","year":"2022","journal-title":"BMC Neurol."},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"191-202","DOI":"10.1038\/s41576-024-00794-y","article-title":"Biobanking with genetics shapes precision medicine and global health.","volume":"26","author":"C Gallagher","year":"2024","journal-title":"Nat Rev Genet."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"389-397","DOI":"10.1111\/joim.12955","article-title":"The advantages of UK Biobank\u2019s open-access strategy for health research.","volume":"286","author":"M Conroy","year":"2019","journal-title":"J Intern Med."},{"key":"ref-16","doi-asserted-by":"publisher","first-page":"203-209","DOI":"10.1038\/s41586-018-0579-z","article-title":"The UK Biobank resource with deep phenotyping and genomic data.","volume":"562","author":"C Bycroft","year":"2018","journal-title":"Nature."},{"key":"ref-17","article-title":"About our data","year":"2024"},{"key":"ref-18","doi-asserted-by":"publisher","first-page":"1026-1034","DOI":"10.1093\/aje\/kwx246","article-title":"Comparison of sociodemographic and health-related characteristics of UK Biobank participants with those of the general population.","volume":"186","author":"A Fry","year":"2017","journal-title":"Am J Epidemiol."},{"key":"ref-19","doi-asserted-by":"publisher","first-page":"527-532","DOI":"10.1038\/s41586-021-03855-y","article-title":"Rare variant contribution to human disease in 281,104 UK Biobank exomes.","volume":"597","author":"Q Wang","year":"2021","journal-title":"Nature."},{"key":"ref-20","doi-asserted-by":"publisher","first-page":"362-369","DOI":"10.1016\/j.bbi.2022.03.010","article-title":"Genetic association study in Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (ME\/CFS) identifies several potential risk loci.","volume":"102","author":"R 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prevalence and recognition.","volume":"194","author":"H Cho","year":"2009","journal-title":"Br J Psychiatry."},{"key":"ref-29","doi-asserted-by":"publisher","first-page":"1449-1455","DOI":"10.2105\/ajph.87.9.1449","article-title":"The prevalence and morbidity of chronic fatigue and Chronic Fatigue Syndrome: a prospective primary care study.","volume":"87","author":"S Wessely","year":"1997","journal-title":"Am J Public Health."},{"key":"ref-30","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-9-91","article-title":"Prevalence of Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (ME\/CFS) in three regions of England: a repeated cross-sectional study in primary care.","volume":"9","author":"L Nacul","year":"2011","journal-title":"BMC Med."},{"key":"ref-31","article-title":"Unequal access to diagnosis of myalgic encephalomyelitis in England.","author":"G Samms","journal-title":"BMC Public 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UK Biobank Field IDs used in analyses. Extended Data Table 2. Definition of ME\/CFS codes in Primary care records"}],"container-title":["NIHR Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-39\/v1\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-39\/v1\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-39\/v1\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T20:05:07Z","timestamp":1748462707000},"score":1,"resource":{"primary":{"URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-39\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,28]]},"references-count":47,"URL":"https:\/\/doi.org\/10.3310\/nihropenres.13956.1","relation":{"has-review":[{"id-type":"doi","id":"10.3310\/nihropenres.15168.r35428","asserted-by":"subject"},{"id-type":"doi","id":"10.3310\/nihropenres.15168.r35434","asserted-by":"subject"},{"id-type":"doi","id":"10.3310\/nihropenres.15168.r35434","asserted-by":"object"},{"id-type":"doi","id":"10.3310\/nihropenres.15168.r35428","asserted-by":"object"}]},"ISSN":["2633-4402"],"issn-type":[{"value":"2633-4402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,28]]},"assertion":[{"value":"Indexed","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-39\/v1#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.3310\/nihropenres.15168.r35428, Joanna Elson, Newcastle University, Newcastle upon Tyne, England, 28 May 2025, version 1, indexed","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-39\/v1#referee-response-35428","order":0,"name":"referee-response-35428","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.3310\/nihropenres.15168.r35434, Matthias Wielscher, Leonardo Vincenzi, Medical University of Vienna, Vienna, 29 May 2025, version 1, indexed","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-39\/v1#referee-response-35434","order":1,"name":"referee-response-35434","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This project is funded by the National Institute for Health and Care Research (NIHR) and Medical Research Council (MRC), grant number MC_PC_20005. GLS was funded by PhD-level research funding from ME Research UK. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This open access work is licensed under the Open Government Licence v3.0.","order":0,"name":"copyright-info","label":"Copyright"}]}}