Seven genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis: a detailed analysis of gene networks and clinical phenotypes.
OBJECTIVE
Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a multisystem disease, the pathogenesis of which remains undetermined. The authors have recently reported a study of gene expression that identified differential expression of 88 human genes in patients with CFS/ME. Clustering of quantitative PCR (qPCR) data from 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, those genes whose expression differed significantly from that of 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 distinct (metabolic, endocrine, cardiovascular, immunological, inflammatory) 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).


CONCLUSIONS
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 would be expected in a disease with a biological basis.
Department of Cellular and Molecular Medicine, St George's University of London, London, UK. jkerr@sgul.ac.uk
J R
JR
Kerr
B
B
Burke
R
R
Petty
J
J
Gough
D
D
Fear
D L
DL
Mattey
J S
JS
Axford
A G
AG
Dalgleish
D J
DJ
Nutt
D000328:Adult; D001007:Anxiety / Q000235:genetics; D016000:Cluster Analysis; D003863:Depression / Q000235:genetics; D015673:Fatigue Syndrome, Chronic / Q000145:classification* / Q000235:genetics* / Q000523:psychology; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D013577:Syndrome