Researchers
Mauricio Arcos-Burgos, Jorge I Vélez, Mauricio Arcos-Holzinger, Claudio Mastronardi, Mario A Isaza-Ruget, Donald P Lewis, Hardip Patel, Brett A Lidbury
Institutions
Include: University of Antioquia, Medellín, Colombia; The Australian National University, Canberra, Australia
Publication
Diagnostics, 2025; 15(12):1542
Funding
Funded by ME Research UK, with further support from the Harold Stannett Williams–Judith J Mason Foundation (Australia)
Key findings
- Variants in a number of genes were found to be significantly associated with ME/CFS.
- These genes are involved in several processes in the brain, including the generation of new neurons, and have been linked with the development of neurological conditions.
- Further studies are needed to investigate the implications on our understanding of the biology of ME/CFS.
About the study
Several studies have identified genetic factors associated with ME/CFS, implicating genes involved in infection, autoimmunity and neuroendocrine function. However, it has proved difficult to replicate these results from study to study.
The genome of an individual (a complete set of their DNA) can be rapidly analysed from a single sample of tissue using machine automation, and this technology has allowed genome-wide association studies to be undertaken in many different diseases, including the DecodeME study in ME/CFS.
Despite the challenges presented by these kinds of studies – including accessing large numbers of well-defined and clinically assessed patients – they are an important part of uncovering the underlying causes of the disease.
Prof. Brett Lidbury at the Australian National University in Canberra, and colleagues at several other centres in Australia and Colombia, have been conducting an ongoing programme to find biomarkers for ME/CFS using a range of sources – bioinformatics, genetics and pathological testing.
What did they do?
In this paper in the journal, Diagnostics, the team presents an analysis of the whole-exome sequences (i.e. all the regions of genes that provide instructions for making proteins) of 77 people with ME/CFS.
Importantly, all the participants were assessed, diagnosed and supported in a specialist ME/CFS clinic by clinicians with extensive experience looking after ME/CFS patients, and only using the Canadian Consensus Criteria–International Consensus Criteria (ICC) for diagnosis.
As part of their assessment, symptom severity was analysed using a number of tools, including measures of fatigue, sleep problems, and depression and anxiety.
DNA samples obtained from ME/CFS patients and control subjects were evaluated using next-generation sequencing, bioinformatics analysis and genome-wide analysis to identify genetic variants associated with ME/CFS.
In addition, any positive associations were then tested in an independent cohort of patients, to ensure the findings could be replicated.
What did they find?
Variants in a number of genes were significantly associated with ME/CFS, compared with a matched population.
These included genes belonging to the Neuroblastoma Breakpoint Family, specifically NBPF1, NBPF10 and NBPF16. These genes are involved in several processes in the brain – including the generation of new neurons in the cerebral cortex – and in the development of neuroblastoma, a type of cancer affecting the nerve tissue. Interestingly, variants in these genes have also been linked with several neurological conditions.
Other genetic variants associated with ME/CFS were detected in the ATR, RSPH10B, ADGRE5-CD97 and NTRK2genes, among others.
Importantly, many of these findings were backed up by analyses in an independent cohort of patients, and the researchers emphasise the need for further studies to look at their implications on the development of ME/CFS.
