DecodeME Genetic Study: Immune and Neuronal Dysregulation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Prof. Dr. Chris Ponting presented the latest findings from DecodeME, the largest genome-wide association study (GWAS) of ME/CFS conducted to date. The study enrolled over 20,000 participants, of whom approximately 18,000 provided saliva samples and 15,500 were included in the genetic analyses. The results confirm that ME/CFS is a polygenic disease, with eight genomic regions showing statistically significant associations. A particularly important finding is that the estimated heritability of ME/CFS concentrates in neural tissues — rather than in the peripheral immune system or other organ systems. Consistent results were observed in fibromyalgia GWAS analyses. No human leukocyte antigen (HLA) association was detected, which would have pointed to a classical adaptive autoimmune mechanism; however, Ponting noted that long-read sequencing of the HLA region will be required to resolve this question definitively. Current data show no evidence of a genetic sex bias in ME/CFS — a finding also reported for fibromyalgia — leaving the marked female predominance in prevalence unexplained at the genetic level. Ponting outlined plans for the next major phase: whole-genome long-read sequencing of approximately 6,000 samples using Nanopore technology, aimed at capturing rare variants and structural changes and identifying the true causal genes. BTN2A1 was highlighted as a leading candidate gene, showing consistent signals across both common-variant and rare-variant analyses. Funding for this project extension — "Sequence ME and Long COVID" — has since been secured. He closed by emphasising that DecodeME was designed from the outset as a co-production with people living with ME/CFS, patient advocacy groups, and charities. Ponting reaffirmed the team's commitment to open data sharing and encouraged research groups to request individual-level data.