No replication of previously reported association with genetic variants in the T cell receptor alpha (TRA) locus for myalgic encephalomyelitis/chronic fatigue  syndrome (ME/CFS).

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease with a variety of symptoms such as post-exertional malaise, fatigue, and pain, but where  aetiology and pathogenesis are unknown. An increasing number of studies have  implicated the involvement of the immune system in ME/CFS. Furthermore, a  hereditary component is suggested by the reported increased risk for disease in  relatives, and genetic association studies are being performed to identify  potential risk variants. We recently reported an association with the  immunologically important human leucocyte antigen (HLA) genes HLA-C and HLA-DQB1  in ME/CFS. Furthermore, a genome-wide genetic association study in 42 ME/CFS  patients reported significant association signals with two variants in the T cell  receptor alpha (TRA) locus (P value <5 × 10(-8)). As the T cell receptors  interact with the HLA molecules, we aimed to replicate the previously reported  findings in the TRA locus using a large Norwegian ME/CFS cohort (409 cases and  810 controls) and data from the UK biobank (2105 cases and 4786 controls). We  investigated numerous SNPs in the TRA locus, including the two previously  ME/CFS-associated variants, rs11157573 and rs17255510. No associations were  observed in the Norwegian cohort, and there was no significant association with  the two previously reported SNPs in any of the cohorts. However, other SNPs  showed signs of association (P value <0.05) in the UK Biobank cohort and  meta-analyses of Norwegian and UK biobank cohorts, but none survived correction  for multiple testing. Hence, our research did not identify any reliable  associations with variants in the TRA locus.