Genetic association study in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) identifies several potential ris... (Hajdarevic et al, 2022)

Genetic association study in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) identifies several potential risk loci
Hajdarevic et al, 2022


Riad Hajdarevic
Asgeir Lande
Jesper Mehlsen
Anne Rydland
Daisy D.Sosa
Elin B.Strand
Olav Mella
Flemming Pociot
Øystein Fluge
Benedicte A.Lie
Marte K.Viken


Largest ME/CFS genetic study to date.

Three different cohorts totaling more than 2500 patients.

First Immunochip study in ME/CFS.

Possible implication of TPPP genetic region.


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=8.5x10-7), 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.

The study:


Senior Member
"We searched through a haystack, and found a couple of straws that were sorta kinda resembling needles..."

Well, negative findings are important too.

Rufous McKinney

Senior Member
seems to be saying the largest cohort ever is still not large enough as the study did not have enough power.
Is this study inconsistent with the metabolic trap hypothesis wrt the prevalence of mutations in the ido2 gene?
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