title: Use of single-nucleotide polymorphisms (SNPs) to distinguish gene expression subtypes of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).
abstract: OBJECTIVE
  We have reported gene expression changes in patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and the fact that such gene expression data can be used to identify subtypes of CFS/ME with distinct clinical phenotypes. Due to the difficulties in using a comparative gene expression method as an aid to CFS/ME disease and subtype-specific diagnosis, we have attempted to develop such a method based on single-nucleotide polymorphism (SNP) analysis.
  
  
  METHODS
  To identify SNP allele associations with CFS/ME and CFS/ME subtypes, we tested genomic DNA of patients with CFS/ME (n=108), patients with endogenous depression (n=17) and normal blood donors (n=68) for 504 human SNP alleles located within 88 CFS-associated human genes using the SNP Genotyping GoldenGate Assay (Illumina, San Diego, California, USA). 360 ancestry informative markers (AIM) were also examined.
  
  
  RESULTS
  21 SNPs were significantly associated with CFS/ME compared with depression and normal groups. 148 SNP alleles had a significant association with one or more CFS/ME subtypes. For each subtype, associated SNPs tended to be grouped together within particular genes. AIM SNPs indicated that 4 subjects were of Asian origin while the remainder were Caucasian. Hierarchical clustering of AIM data revealed the relatedness between 2 couples of patients with CFS only and confirmed the overall heterogeneity of all subjects.
  
  
  CONCLUSIONS
  This study provides evidence that human SNPs located within CFS/ME associated genes are associated with particular genomic subtypes of CFS/ME. Further work is required to develop this into a clinically useful subtype-specific diagnostic test.
authors.affiliation: CFS Group, Department of Cellular & Molecular Medicine, St George's University of London, London, UK.
authors.forename: Nana
authors.initials: N
authors.lastname: Shimosako
authors.affiliation: CFS Group, Department of Cellular & Molecular Medicine, St George's University of London, London, UK Escuela de Medicina y Ciencias de Salud, Universidad del Rosario, Bogota, Colombia.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Kerr
mesh_terms: D000328:Adult; D016000:Cluster Analysis; D003863:Depression / Q000235:genetics; D015673:Fatigue Syndrome, Chronic / Q000145:classification* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D059467:Transcriptome
keywords: BIOLOGICAL SCIENCES; EPIDEMIOLOGY; GENETICS