Genetic architecture of chronic fatigue syndrome

Project description

Currently, there is no consensus on the genetic foundations of ME/CFS, although its heritability estimated at up to 50%. While a large-scale Genome-Wide Association Studies (GWAS) is ongoing in a dedicated ME/CFS cohort in the UK (DecodeME), our project will complement this by focusing on rare genetic variants. Thus, the aim of this research project is to provide a list of causal genes for ME/CFS to facilitate further testing and characterisation in collaboration with clinical researchers and wet lab biologists. 

This opportunity arises from the recent availability of whole genome sequencing data from large-scale biobanks such as the UK ME/CFS Biobank and the NIH All of Us Research Program Biobank. The investigators can now categorise all protein-altering variants within a gene or other genomic structures like transcription factor binding sites and evaluate their collective impact on ME/CFS. They will utilise the International Consensus Criteria (ICC) to define cases, however the investigators will also conduct sensitivity analyses around the phenotype definition, and extend their analyses to include long COVID phenotypes within the cohorts mentioned above.

The investigators' primary analysis will be a meta-analysis of data from the UK ME/CFS Biobank and the NIH All of Us Biobank, which they will, depending on availability, also attempt to replicate using imputed data from the DecodeME cohort. This will not only provide the most extensive analysis of rare variants in ME/CFS to date enhancing the knowledge of the condition's causal genes and pathways, but it will also establish a dataspace and collaborative framework for clustering, factor analysis, and other exploratory and epidemiological studies, which the investigators think are essential to fully understand this complex condition. These analyses could also inform subsequent rounds of genetic association tests. Ultimately, the outcomes of these tests may enable stratification of patients and facilitate the categorisation of patients into specific subgroups.

(Description adapted from project website: see link above)