Research using data from the DecodeME study found no meaningful evidence that mutations in the DHCR7 gene, linked to the production and utilisation of cholesterol and vitamin D in the body, increase the risk of ME/CFS.
Prior to initiating the study, the researchers noted that dysfunction in the production and utilisation of cholesterol, and deficiency in vitamin D, may play a role in the complex disease mechanisms underpinning illnesses such as ME/CFS and multiple sclerosis.
Building on this, the team identified a gene called DHCR7 that produces an enzyme — a specialised protein that speeds up chemical reactions in cells without being used up — that:
- Plays a crucial role in the final step of cholesterol production in the body,
- Influences the levels of a compound in the skin, known as provitamin D, which is converted into vitamin D when exposed to sunlight outdoors.
Although uncommon, when a person inherits two altered copies (mutations) of the DHCR7 gene, a syndrome called “Smith-Lemli-Opitz syndrome (SLOS)” develops. SLOS is a rare genetic disorder impacting multiple systems of the body. It is characterised by low cholesterol levels, intellectual disability, behavioural issues, and physical malformations like fused toes, cleft palate, and microcephaly. Notably, cholesterol deficiency disrupts myelination of nerve fibres contributing to the neurological symptoms of SLOS.
While the inheritance of two altered copies of the gene is extremely rare, having one altered copy affects significantly more people in the population. The research team hypothesised that although people with one altered copy of the gene do not have SLOS, they may have subclinical levels of disruption to cholesterol and vitamin D metabolism, which may be a risk factor for the development of diseases such as ME/CFS, and MS.
Despite the plausible theoretical link and the large sample size of over 15,000 people with ME/CFS and nearly 260,000 healthy controls, the team found no meaningful evidence that mutations in the DHCR7 gene increase the risk of ME/CFS. However, this result needs to be confirmed in other study populations before drawing firm conclusions.
Notably, the team suggested that cholesterol metabolism in people with ME/CFS deserves closer attention. Rather than focusing only on genetics, future studies could look at more subtle changes—such as directly measuring levels of cholesterol-related compounds in those with ME/CFS and comparing them with those in healthy individuals.
The researchers also stress the importance of publishing studies with negative or null findings. Doing so helps avoid publication bias—a tendency for journals to favour studies with positive, statistically significant results—ensuring that the scientific record more accurately reflects the full range of evidence.
