Genetics of chronic fatigue syndrome

A 2011 study by F. Albright, K. Light, A. Light, L. Bateman, and L. Cannon-Albright showed evidence of a heritable contribution to CFS. Using the extensive records of the Utah Population Database (UPDB), the study "shows clear evidence of significant excess familial clustering and significantly elevated risks for CFS among first, second, and third degree relatives of CFS cases. The results strongly support a genetic contribution to predisposition to CFS as it is currently defined and diagnosed by clinicians in Utah." Increased outbreak rates in first degree relatives are not automatically assumed to be genetic because the first degree relatives often share the same lifestyle and environment. However, a significantly increased incidence (95% confidence interval) in second and third degree relatives strongly indicated a genetic contribution to CFS, given the much lower likelihood of these relatives sharing common risks and environments.

A 2001 study in the UK showed "there were significantly higher rates of CFS in the relatives of CFS cases compared with the relatives of control subjects." Three twin studies (one in Australia, one in Washington, US, both in 2001, and one in the UK in 2007) showed that the correlations for prolonged and chronic fatigue were significantly higher in monozygotic than dizygotic twins for each definition of chronic fatigue syndrome.

One study showed that patients with mitochondrial DNA from certain haplogroups correlated with variations in gastrointestinal, neurological, and inflammatory symptoms.

Notable Studies

• 2016, Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue syndrome (FULL TEXT)

  Abstract - "Myalgic encephalomyelitis, also known as chronic fatigue syndrome or ME/CFS, is a multifactorial and debilitating disease that has an impact on over 4 million people in the United States alone. The pathogenesis of ME/CFS remains largely unknown; however, a genetic predisposition has been suggested. In the present study, we used a DNA single-nucleotide polymorphism (SNP) chip representing over 906,600 known SNPs to analyze DNA from ME/CFS subjects and healthy controls. To the best of our knowledge, this study represents the most comprehensive genome-wide association study (GWAS) of an ME/CFS cohort conducted to date. Here 442 SNPs were identified as candidates for association with ME/CFS (adjusted P-value<0.05). Whereas the majority of these SNPs are represented in non-coding regions of the genome, 12 SNPs were identified in the coding region of their respective gene. Among these, two candidate SNPs resulted in missense substitutions, one in a pattern recognition receptor and the other in an uncharacterized coiled-coil domain-containing protein. We also identified five SNPs that cluster in the non-coding regions of T-cell receptor loci. Further examination of these polymorphisms may help identify contributing factors to the pathophysiology of ME/CFS, as well as categorize potential targets for medical intervention strategies.

• 2016, Mitochondrial DNA variants correlate with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (Maureen Hanson, January 20). See also Mitochondrial DNA and ME/CFS - A Guide to the Hanson Lab's 2016 JTM Publication.

Media Coverage

• 2016, Genome-wide associations
• 2016, New study found SNPs for some symptoms (CFS Remission, January 23)

See also

• Mitochondria

genome an organism's complete set of DNA, including all of its genes

myalgic encephalomyelitis (M.E.) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

single nucleotide polymorphism (SNP) - A single nucleotide polymorphism (SNP, pronounced "snip") is a potential genetic mutation that occurs in a single spot in the human genome; a difference in a single DNA building block. SNPs are often represented by an "rs" number, such as "rs53576".

genome an organism's complete set of DNA, including all of its genes

T cell A type of white blood cell which is mostly produced or matured in the thymus gland (hence T-cell) and is involved in the adaptive immune response on a cellular level. Also known as a T lymphocyte. (Learn more: www.youtube.com)

somatic symptom disorder A psychiatric term to describe an alleged condition whereby a person's thoughts somehow cause physical symptoms. The actual existence of such a condition is highly controversial, due to a lack of scientific evidence. It is related to other psychiatric terms, such as "psychosomatic", "neurasthenia", and "hysteria". Older terms include "somatization", "somatoform disorder", and "conversion disorder". Such terms refer to a scientifically-unsupported theory that claims that a wide range of physical symptoms can be created by the human mind, a theory which has been criticized as "mind over matter" parapsychology, a pseudoscience.

etiology The cause of origin, especially of a disease.