title: Mitochondrial DNA variants correlate with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome.
abstract: BACKGROUND
  Mitochondrial dysfunction has been hypothesized to occur in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a disease characterized by fatigue, cognitive difficulties, pain, malaise, and exercise intolerance. We investigated whether haplogroup, single nucleotide polymorphisms (SNPs), or heteroplasmy of mitochondrial DNA (mtDNA) were associated with health status and/or symptoms.
  
  
  METHODS
  Illumina sequencing of PCR-amplified mtDNA was performed to analyze sequence and extent of heteroplasmy of mtDNAs of 193 cases and 196 age- and gender-matched controls from DNA samples collected by the Chronic Fatigue Initiative. Association testing was carried out to examine possible correlations of mitochondrial sequences with case/control status and symptom constellation and severity as reported by subjects on Short Form-36 and DePaul Symptom Questionnaires.
  
  
  RESULTS
  No ME/CFS subject exhibited known disease-causing mtDNA mutations. Extent of heteroplasmy was low in all subjects. Although no association between mtDNA SNPs and ME/CFS vs. healthy status was observed, haplogroups J, U and H as well as eight SNPs in ME/CFS cases were significantly associated with individual symptoms, symptom clusters, or symptom severity.
  
  
  CONCLUSIONS
  Analysis of mitochondrial genomes in ME/CFS cases indicates that individuals of a certain haplogroup or carrying specific SNPs are more likely to exhibit certain neurological, inflammatory, and/or gastrointestinal symptoms. No increase in susceptibility to ME/CFS of individuals carrying particular mitochondrial genomes or SNPs was observed.
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY, 14853, USA. pdb87@cornell.edu.
authors.forename: Paul
authors.initials: P
authors.lastname: Billing-Ross
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, 14853, USA. ag297@cornell.edu.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Germain
authors.affiliation: Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY, 14853, USA. ky297@cornell.edu.
authors.forename: Kaixiong
authors.initials: K
authors.lastname: Ye
authors.affiliation: Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY, 14853, USA. ak735@cornell.edu.
authors.forename: Alon
authors.initials: A
authors.lastname: Keinan
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY, 14853, USA. zg27@cornell.edu.
authors.forename: Zhenglong
authors.initials: Z
authors.lastname: Gu
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, 14853, USA. mrh5@cornell.edu.
authors.forename: Maureen R
authors.initials: MR
authors.lastname: Hanson
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D015673:Fatigue Syndrome, Chronic / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; D005819:Genetic Markers