Seven genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis: a detailed analysis of gene networks and clinical phenotypes

Aim: Chronic fatigue syndrome/myalgic (CFS/ME) is a multisystem disease, the pathogenesis which remains undetermined. The authors have reported a study of gene expression that identified differential expression of 88 human genes in patients CFS/ME. Clustering of quantitative PCR (qPCR) data patients with CFS/ME revealed seven distinct subtypes with distinct differences in Medical Outcomes Survey Short Form-36 scores, clinical phenotypes and severity. Methods: In this study, for each CFS/ME subtype, genes whose expression differed significantly from that normal blood donors were identified, and then gene interactions, disease associations and molecular and cellular functions of those gene sets were determined. Genomic analysis was then related to clinical data for each CFS/ME subtype. Results: Genomic analysis revealed some common (neurological, haematological, cancer) and some (metabolic, endocrine, cardiovascular, immunological, inflammatory) disease associations among the Subtypes 1, 2 and 7 were the most severe, and subtype was the mildest. Clinical features of each subtype as follows: subtype 1 (cognitive, musculoskeletal, anxiety/depression); subtype 2 (musculoskeletal, pain, anxiety/depression); subtype 3 (mild); subtype 4 (subtype 5 (musculoskeletal, gastrointestinal); 6 (postexertional); subtype 7 (pain, infectious, musculoskeletal, sleep, neurological, gastrointestinal, neurocognitive, anxiety/depression). Conclusion: It was particularly interesting that in the seven genomically derived subtypes there were distinct clinical syndromes, and that those which were most severe were also those with anxiety/depression, as be expected in a disease with a biological basis.