Genetic association study in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) identifies several potential risk loci.

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease of unknown etiology and pathogenesis, which manifests in a variety of symptoms like  post-exertional malaise, brain fog, fatigue and pain. Hereditability is suggested  by an increased disease risk in relatives, however, genome-wide association  studies in ME/CFS have been limited by small sample sizes and broad diagnostic  criteria, therefore no established risk loci exist to date. In this study, we  have analyzed three ME/CFS cohorts: a Norwegian discovery cohort (N = 427), a  Danish replication cohort (N = 460) and a replication dataset from the UK biobank  (N = 2105). To the best of our knowledge, this is the first ME/CFS genome-wide  association study of this magnitude incorporating 2532 patients for the  genome-wide analyses and 460 patients for a targeted analysis. Even so, we did  not find any ME/CFS risk loci displaying genome-wide significance. In the  Norwegian discovery cohort, the TPPP gene region showed the most significant  association (rs115523291, P = 8.5 × 10(-7)), but we could not replicate the top  SNP. However, several other SNPs in the TPPP gene identified in the Norwegian  discovery cohort showed modest association signals in the self-reported UK  biobank CFS cohort, which was also present in the combined analysis of the  Norwegian and UK biobank cohorts, TPPP (rs139264145; P = 0.00004). Interestingly,  TPPP is expressed in brain tissues, hence it will be interesting to see whether  this association, with time, will be verified in even larger cohorts. Taken  together our study, despite being the largest to date, could not establish any  ME/CFS risk loci, but comprises data for future studies to accumulate the power  needed to reach genome-wide significance.