Preprint Initial findings from the DecodeME genome-wide association study of myalgic encephalomyelitis/chronic fatigue syndrome, 2025, DecodeMe Collaboration

[Jonathan Edwards]

A question that remains is what exactly is causing the increased risk in women. Is it genetic variants on the X chromosome, hormonal or immune differences?

I don't think the 'increased risk in women' - i.e. why women have more ME/CFS than men - can be due to genetic variants of the X chromosomes because any variants will be shared out equally to both men and women. Genetic variants on the X chromosome may explain why women with ME/CFS have it and women without ME/CFS don't but that is a separate issue.

And we almost certainly cannot separate hormonal from immune issues because immune differences are very likely dependent on cumulative hormonal environment over many years, with changes at menarche and menopause. There might be a polymorphism in a gene for an immune receptor that is directly influenced in expression level by a single gene on the X chromosome with dosage effect (double for women). It that polymorphism was skewed differently in women with ME/CFS from women without ME/CFS we would have something meaty to work on but this may be wishful thinking.