Genetics of chronic fatigue syndrome

The genetics of chronic fatigue syndrome is an area of research as ME/CFS has been observed in families. It is unknown if there is a genetic link or common environmental exposure (infectious or toxic). Studies of twins show higher rates of ME/CFS in identical than fraternal twins. The Centers for Disease Control and Prevention (CDC) notes that specific genetic associations have not been established.

A 2011 study by Albright et al showed evidence of a heritable contribution to chronic fatigue syndrome (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

 * 2001, A twin study of chronic fatigue (Abstract)
 * 2006, Combinations of single nucleotide polymorphisms in neuroendocrine effector and receptor genes Three genes were found to be common in a group of people with Chronic Fatigue Syndrome compared to the general population; TPH2 - neuronal tryptophan hydroxylase, COMT - catechol-O-methyltransferase, and NR3C1 - nuclear receptor subfamily 3, group C, member 1 glucocorticoid receptor, together these three have an accuracy of 76%.
 * 2011, Evidence for a heritable predisposition to Chronic Fatigue Syndrome (Abstract)
 * 2011, Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome
 * 2016, Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue syndrome (Full Text)
 * 2016, Mitochondrial DNA variants correlate with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (Abstract)
 * 2018, Identification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-associated DNA methylation patterns (Abstract)
 * 2018, Genome-epigenome interactions associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. (Abstract)
 * 2019, Associations between clinical symptoms, plasma norepinephrine and deregulated immune gene networks in subgroups of adolescent with Chronic Fatigue Syndrome. (Abstract)
 * 2019 - Genetic Predisposition for Immune System, Hormone, and Metabolic Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Pilot Study (Full text)

Media Coverage

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

Learn more

 * Mitochondrial DNA and ME/CFS - A Guide to the Hanson Lab's - 2016 JTM Publication