Seven genomic subtypes of Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (CFS/ME): a detailed analysis of gene networks and clinical phenotypes
Jonathan R Kerr,1,2 Beverley Burke,1* Robert Petty,1* John Gough,1,2 David Fear,3 Derek L Mattey,4 John S Axford,1,2 Angus G Dalgleish,1 David J Nutt.5
1Department of Cellular & Molecular Medicine, St George’s University of London, London, UK; Sir Joseph Hotung Centre for Musculoskeletal Disorders; 3Dept of Asthma, Allergy and Respiratory Sciences, King’s College London, London, UK; 4Staffordshire Rheumatology Centre, Stoke on Trent, UK; 5Psychopharmacology Unit, Dept of Community Based Medicine, University of Bristol, Bristol, UK.
*Robert Petty and Beverley Burke made equal contributions to this paper.
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, 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). It is particularly interesting that in these genomically derived subtypes, there were distinct clinical syndromes and that those which
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