Approved Research

Testing Hypotheses for Genetic Predisposition to Chronic Fatigue Syndrome (CFS) in a UK Patient Population

Lay summary

Chronic Fatigue Syndrome (CFS) is debilitating disease affecting approximately one person in 100.  Last year we published a new theory for the cause of CFS called the IDO metabolic trap. This theory involves common mutations in a gene called IDO2, which is the first step of the kynurenine pathway of tryptophan metabolism. These mutations, when confronted with a severe stress such as infection or trauma, open the door to an abnormal metabolic state where almost no kynurenine can be produced. This can result in autoimmunity, cognitive problems, and intestinal problems. We have tested this theory in 73 CFS patients and found that all but one of them had damaging mutations in IDO2, but this test needs to be repeated in a larger group of patients. Our aims are:

1. Test the IDO metabolic trap theory using genetic data on more than 2000 CFS patients in UKBiobank.

2. Check for Hardy-Weinberg disequilibrium in the patient group, check for statistical significance.

3.  Repeat these tests for other common damaging mutations found in our small patient group.

Project duration: 7 months

Public health impact: CFS is a devastating disease that runs in families. We will test as many as 93 common damaging mutations as explanations for this heritability, and for possible disease mechanisms. This proposal, therefore, offers a low-risk, high potential reward for CFS research.