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Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
An unbiased metagenomic search for infectious agents using monozygotic twins discordant for chronic fatigue
Patrick F Sullivan1, Tobias Allander, Fredrik Lysholm
1Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. pfsulliv@med.unc.edu
Background:
Chronic fatigue syndrome is an idiopathic syndrome widely suspected of having an infectious or immune etiology. We applied an unbiased metagenomic approach to try to identify known or novel infectious agents in the serum of 45 cases with chronic fatigue syndrome or idiopathic chronic fatigue. Controls were the unaffected monozygotic co-twins of cases, and serum samples were obtained at the same place and time.
Results:
No novel DNA or RNA viral signatures were confidently identified. Four affected twins and no unaffected twins evidenced viremia with GB virus C (8.9% vs. 0%, p = 0.019), and one affected twin had previously undetected hepatitis C viremia. An excess of GB virus C viremia in cases with chronic fatigue requires confirmation.
Conclusions:
Current, impairing chronic fatigue was not robustly associated with viremia detectable in serum.
Insights
This study investigated infectious agents in chronic fatigue syndrome (CFS) patients. While no novel viruses were found, a higher prevalence of GB virus C viremia was observed in affected individuals, warranting further research.
Area of Science:
- Infectious disease
- Virology
- Immunology
Background:
- Chronic fatigue syndrome (CFS) is a complex, idiopathic condition with suspected infectious or immune origins.
- An unbiased metagenomic approach was employed to identify infectious agents in CFS patients.
- Serum samples were collected from 45 CFS cases and their unaffected monozygotic co-twin controls.
Purpose of the Study:
- To identify known or novel infectious agents in the serum of individuals with chronic fatigue syndrome or idiopathic chronic fatigue.
- To investigate potential viral etiologies of CFS using a comprehensive metagenomic analysis.
Main Methods:
- Unbiased metagenomic sequencing of serum samples from CFS cases and controls.
- Comparative analysis to identify differential presence of viral signatures.
- Statistical analysis to determine the significance of observed viral associations.
Main Results:
- No novel DNA or RNA viral signatures were definitively identified in CFS patients.
- GB virus C (GBV-C) viremia was detected in 8.9% of affected twins versus 0% of unaffected twins (p = 0.019).
- One affected twin showed previously undetected hepatitis C viremia; further confirmation of GBV-C excess in CFS is needed.
Conclusions:
- Serum viremia detectable by metagenomics was not robustly associated with chronic, impairing fatigue.
- The observed excess of GB virus C viremia in CFS cases requires further investigation and validation.
- The etiology of chronic fatigue syndrome remains multifactorial, with current findings not strongly supporting viremia as a primary driver.
