Get the latest Science News and Discoveries

Replicated blood-based biomarkers for Myalgic Encephalomyelitis not explicable by inactivity

Myalgic Encephalomyelitis (ME; sometimes referred to as chronic fatigue syndrome) is a relatively common and female-biased disease of unknown pathogenesis that profoundly decreases patients' health-related quality-of-life. ME diagnosis is hindered by the absence of robustly-defined and specific biomarkers that are easily measured from available sources such as blood, and unaffected by ME patients' low level of physical activity. Previous studies of blood biomarkers have not yielded replicated results, perhaps due to low study sample sizes (n<100). Here, we use UK Biobank (UKB) data for up to 1,455 ME cases and 131,303 population controls to discover hundreds of molecular and cellular blood traits that differ significantly between cases and controls. Importantly, 116 of these traits are replicated, as they are significant for both female and male cohorts. Our analysis used semi-parametric efficient estimators, an initial Super Learner fit followed by a one-step correction, three types of mediators, and natural direct and indirect estimands, to decompose the average effect of ME status on molecular and cellular traits. Strikingly, these trait differences cannot be explained by ME cases' restricted activity. Of 3,237 traits considered, ME status had a significant effect on only one, via the "Duration of walk" (UKB field 874) mediator. By contrast, ME status had a significant direct effect on 290 traits (9%). As expected, these effects became more significant with increased stringency of case and control definition. Significant female and male traits were indicative of chronic inflammation, insulin resistance and liver disease. Individually, significant effects on blood traits, however, were not sufficient to cleanly distinguish cases from controls. Nevertheless, their large number, lack of sex-bias, and strong significance, despite the 'healthy volunteer' selection bias of UKB participants, keep alive the future ambition of a blood-based biomarker panel for accurate ME diagnosis. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by a grant for PhD-level research to GLS from ME Research UK (SCIO charity number SCO36942). This research has been conducted using the UK Biobank Resource under Application Number 76173. Access to this data was funded by the National Institute for Health and Care Research (NIHR) and Medical Research Council (MRC) under grant number MC\_PC\_20005. AK was supported by a Langmuir Talent Development Fellowship from the Institute of Genetics and Cancer, and a philanthropic donation from Hugh and Josseline Langmuir. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Only existing public datasets (UK Biobank) were used. In accordance with UK Biobank regulations, we have included the statement "This research has been conducted using the UK Biobank Resource under Application Number 76173." in the manuscript's Acknowledgement section, and notified the access management team of UK Biobank at least 2 weeks prior to this submission (specifically, on 7 August 2024). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes No data has been produced. All data is from UK Biobank.

None

Get the Android app