Genetic risk factors of ME/CFS: a critical review
Doctors with M.E. Honorary Fellow, Professor Chris Ponting co-authors a review that highlights the need for large genome-wide association studies, such as the much anticipated DecodeME project. Such studies are required to identify possible genetic risk factors in ME/CFS, as this could improve our understanding and drive the development of novel therapeutic strategies.
“A genome-wide association study (GWAS) is ideal for discovering genetic causes of disease and new biology particularly when disease aetiology is unknown, as is the case for ME/CFS. This is not just because it is comprehensive but because its results are not influenced by pre-existing biological assumptions or hypotheses.”
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex multisystem illness that lacks effective therapy and a biomedical understanding of its causes. Despite a prevalence of ∼0.2–0.4% and its high public health burden, and evidence that it has a heritable component, ME/CFS has not yet benefited from the advances in technology and analytical tools that have improved our understanding of many other complex diseases. Here we critically review existing evidence that genetic factors alter ME/CFS risk before concluding that most ME/CFS candidate gene associations are not replicated by the larger CFS cohort within the UK Biobank. Multiple genome-wide association studies of this cohort also have not yielded consistently significant associations. Ahead of upcoming larger genome-wide association studies, we discuss how these could generate new lines of enquiry into the DNA variants, genes and cell types that are causally involved in ME/CFS disease.
Dibble, JJ., McGrath, SJ., Ponting, CP. Genetic risk factors of ME/CFS: a critical review. Human Molecular Genetics 2020; 29(R1):R117-R124. https://doi.org/10.1093/hmg/ddaa169
Prof. Chris Ponting
Medical Bioinformatics Chair, University of Edinburgh, MRC Human Genetics Unit Group Leader. Associate Faculty, Wellcome Trust Sanger Institute, Fellow, Academy of Medical Sciences, Fellow, Royal Society of Edinburgh