Replicated blood-based biomarkers for myalgic encephalomyelitis not explicable by inactivity
Abstract Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a common female-biased disease. ME/CFS diagnosis is hindered by the absence of biomarkers that are unaffected by patients’ low physical activity level. Our analysis used semi-parametric efficient estimators, an initial Super Lea...
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| Format: | Article |
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Springer Nature
2025-06-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.1038/s44321-025-00258-8 |
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| author | Sjoerd Viktor Beentjes Artur Miralles Méharon Julia Kaczmarczyk Amanda Cassar Gemma Louise Samms Nima S Hejazi Ava Khamseh Chris P Ponting |
| author_facet | Sjoerd Viktor Beentjes Artur Miralles Méharon Julia Kaczmarczyk Amanda Cassar Gemma Louise Samms Nima S Hejazi Ava Khamseh Chris P Ponting |
| author_sort | Sjoerd Viktor Beentjes |
| collection | DOAJ |
| description | Abstract Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a common female-biased disease. ME/CFS diagnosis is hindered by the absence of biomarkers that are unaffected by patients’ low physical activity level. Our analysis used semi-parametric efficient estimators, an initial Super Learner fit followed by a one-step correction, three mediators, and natural direct and indirect estimands, to decompose the average effect of ME/CFS status on molecular and cellular traits. For this, we used UK Biobank data for up to 1455 ME/CFS cases and 131,303 controls. Hundreds of traits differed significantly between cases and controls, including 116 significant for both female and male cohorts. These were indicative of chronic inflammation, insulin resistance and liver disease. Nine of 14 traits were replicated in the smaller All-of-Us cohort. Results cannot be explained by restricted activity: via an activity mediator, ME/CFS status significantly affected only 1 of 3237 traits. Individuals with post-exertional malaise show stronger biomarker differences. Single traits could not cleanly distinguish cases from controls. Nevertheless, these results keep alive the future ambition of a blood-based biomarker panel for accurate ME/CFS diagnosis. |
| format | Article |
| id | doaj-art-08169c5df2164cd58fadde1693f3d79b |
| institution | Kabale University |
| issn | 1757-4684 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Springer Nature |
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| series | EMBO Molecular Medicine |
| spelling | doaj-art-08169c5df2164cd58fadde1693f3d79b2025-08-20T03:46:25ZengSpringer NatureEMBO Molecular Medicine1757-46842025-06-011771868189110.1038/s44321-025-00258-8Replicated blood-based biomarkers for myalgic encephalomyelitis not explicable by inactivitySjoerd Viktor Beentjes0Artur Miralles Méharon1Julia Kaczmarczyk2Amanda Cassar3Gemma Louise Samms4Nima S Hejazi5Ava Khamseh6Chris P Ponting7School of Mathematics and Maxwell Institute for Mathematical Sciences, University of EdinburghSchool of Informatics, University of EdinburghSchool of Mathematics and Maxwell Institute for Mathematical Sciences, University of EdinburghSchool of Informatics, University of EdinburghMRC Human Genetics Unit, Institute of Genetics & Cancer, University of EdinburghHarvard T.H. Chan School of Public Health, Department of BiostatisticsMRC Human Genetics Unit, Institute of Genetics & Cancer, University of EdinburghMRC Human Genetics Unit, Institute of Genetics & Cancer, University of EdinburghAbstract Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a common female-biased disease. ME/CFS diagnosis is hindered by the absence of biomarkers that are unaffected by patients’ low physical activity level. Our analysis used semi-parametric efficient estimators, an initial Super Learner fit followed by a one-step correction, three mediators, and natural direct and indirect estimands, to decompose the average effect of ME/CFS status on molecular and cellular traits. For this, we used UK Biobank data for up to 1455 ME/CFS cases and 131,303 controls. Hundreds of traits differed significantly between cases and controls, including 116 significant for both female and male cohorts. These were indicative of chronic inflammation, insulin resistance and liver disease. Nine of 14 traits were replicated in the smaller All-of-Us cohort. Results cannot be explained by restricted activity: via an activity mediator, ME/CFS status significantly affected only 1 of 3237 traits. Individuals with post-exertional malaise show stronger biomarker differences. Single traits could not cleanly distinguish cases from controls. Nevertheless, these results keep alive the future ambition of a blood-based biomarker panel for accurate ME/CFS diagnosis.https://doi.org/10.1038/s44321-025-00258-8Myalgic EncephalomyelitisSemi-parametric Mediation AnalysisPost-exertional MalaiseUK BiobankAll of Us Biobank |
| spellingShingle | Sjoerd Viktor Beentjes Artur Miralles Méharon Julia Kaczmarczyk Amanda Cassar Gemma Louise Samms Nima S Hejazi Ava Khamseh Chris P Ponting Replicated blood-based biomarkers for myalgic encephalomyelitis not explicable by inactivity EMBO Molecular Medicine Myalgic Encephalomyelitis Semi-parametric Mediation Analysis Post-exertional Malaise UK Biobank All of Us Biobank |
| title | Replicated blood-based biomarkers for myalgic encephalomyelitis not explicable by inactivity |
| title_full | Replicated blood-based biomarkers for myalgic encephalomyelitis not explicable by inactivity |
| title_fullStr | Replicated blood-based biomarkers for myalgic encephalomyelitis not explicable by inactivity |
| title_full_unstemmed | Replicated blood-based biomarkers for myalgic encephalomyelitis not explicable by inactivity |
| title_short | Replicated blood-based biomarkers for myalgic encephalomyelitis not explicable by inactivity |
| title_sort | replicated blood based biomarkers for myalgic encephalomyelitis not explicable by inactivity |
| topic | Myalgic Encephalomyelitis Semi-parametric Mediation Analysis Post-exertional Malaise UK Biobank All of Us Biobank |
| url | https://doi.org/10.1038/s44321-025-00258-8 |
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