Seven genomic subtypes of Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (CFS/ME): a detailed analysis of gene networks and clinical phenotypes

Abstract

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