Biological Insights from Genome-Wide Association Studies and Whole Genome Sequencing of [ME/CFS], 2026, Maccallini et al
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Jonathan Edwards
Senior Member (Voting Rights)
Is he the 'citizen scientist' Chris P referred to?
Biological Insights from Genome-Wide Association Studies and Whole Genome Sequencing of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Maccallini, Paolo
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disorder of poorly understood etiology.
We performed a meta-analysis of two European-ancestry ME/CFS genome-wide association studies (GWAS) with no overlap in subjects, DecodeME and Million Veteran Program, comprising a total of 19,470 cases and 699,111 controls. Post-GWAS analyses investigated the association between ME/CFS and specific tissues, cell types, cellular components, and canonical pathways. Findings were independently evaluated for replication against a module of ME/CFS risk genes previously prioritized by machine learning applied to rare coding variants from whole-genome sequencing (WGS) of ME/CFS cases and controls of European ancestry.
Tissue enrichment analysis implicated multiple brain regions and the pituitary, with no peripheral tissue reaching significance, and three survived Bonferroni-corrected replication. Gene-set analysis identified multiple neuronal and synaptic gene sets, several of which were independently replicated, with glutamatergic synapses as the most specific replicated signal. Cell-type analysis identified independent replicated signals in distinct neuronal populations of subcortical and cerebellar regions.
These results suggest a role for synaptic function in specific brain regions in the pathogenesis of ME/CFS, with convergent support from both common and rare variant data. Larger studies are needed to confirm these findings and to identify specific targets for therapeutic intervention.
Web | DOI | Zenodo | Preprint
Maccallini, Paolo
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disorder of poorly understood etiology.
We performed a meta-analysis of two European-ancestry ME/CFS genome-wide association studies (GWAS) with no overlap in subjects, DecodeME and Million Veteran Program, comprising a total of 19,470 cases and 699,111 controls. Post-GWAS analyses investigated the association between ME/CFS and specific tissues, cell types, cellular components, and canonical pathways. Findings were independently evaluated for replication against a module of ME/CFS risk genes previously prioritized by machine learning applied to rare coding variants from whole-genome sequencing (WGS) of ME/CFS cases and controls of European ancestry.
Tissue enrichment analysis implicated multiple brain regions and the pituitary, with no peripheral tissue reaching significance, and three survived Bonferroni-corrected replication. Gene-set analysis identified multiple neuronal and synaptic gene sets, several of which were independently replicated, with glutamatergic synapses as the most specific replicated signal. Cell-type analysis identified independent replicated signals in distinct neuronal populations of subcortical and cerebellar regions.
These results suggest a role for synaptic function in specific brain regions in the pathogenesis of ME/CFS, with convergent support from both common and rare variant data. Larger studies are needed to confirm these findings and to identify specific targets for therapeutic intervention.
Web | DOI | Zenodo | Preprint
Jonathan Edwards
Senior Member (Voting Rights)
Were you aware of this one @James Cox ?