Mitochondrial DNA variants correlate with symptoms in ME/CFS 2016 Billing-Ross et al.

Paper from 2016 by the Hanson group. I wanted to post it here because it had a large sample size (large for ME/CFS research, probably small for genetics research).

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.

https://pubmed.ncbi.nlm.nih.gov/26791940/

 

It's interesting that they managed to recruit 193 cases despite having fairly many with recent acute onsets of under 3 years. Given the problems the intramural study had at recruiting patientsit would be interesting to know how many of these acute onsets were assumed to be infectious and how many were documented to be infectious (in DecodeME the rates were (68%) for confirmed test of glandular fever, 50% for Covid and for other infectious onsets it was very low (26%)).

Not particularly suprising that almost everyone in the age category 61-75 had been ill for longer than 3 years.