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The following is a summary of “A comparison of genome-wide association analyses of persistent symptoms after Lyme disease, fibromyalgia, and myalgic encephalomyelitis – chronic fatigue syndrome,” published in the February 2025 issue of BMC Infectious Diseases by Hirsch et al. 

Researchers conducted a retrospective study to investigate the genetic basis of post-treatment Lyme disease syndrome (PTLDS) and identify potential treatment targets.  

They performed a genome-wide association study (GWAS) on PTLDS using electronic health records (EHR) and genetic data from a linked biorepository in a Pennsylvania health system. The GWAS validity was assessed in fibromyalgia and myalgic encephalomyelitis – chronic fatigue syndrome (ME/CFS) due to hypothesized overlapping pathophysiology. The Logistic regression in SUGEN was used, assuming an additive genetic model and adjusting for age, sex, array, and the first 10 principal components from whole genome genotyping to account for ancestry and relatedness, including all first-degree relationships. The functional mapping and annotation analysis (FUMA) tool was applied to explore top GWAS findings.  

The results showed that among 1,61,875 eligible MyCode participants with genotyping, 3,585 met the criteria for treated Lyme disease. Of these, 695 (19.4%) had PTLDS, while 2,890 served as controls and 2 PTLDS loci met the suggestive significance threshold (P < 5 × 10^-7), with lead variants rs77857587 near IRX1 and rs10833979 near GAS2. The top index single nucleotide polymorphism (SNP), rs77857587, exhibited high linkage disequilibrium with rs111774530, a long-range protein quantitative locus SNP for MARC2 (Mitochondrial Amidoxime Reducing Component 2). Among MyCode participants, 5,041 had fibromyalgia (1,50,599 controls), and 2,268 had (ME/CFS) syndrome  (1,51,594 controls), but the 2 significant PTLDS loci showed no association. 

Investigators concluded that suggestive genetic loci linked to the MARC2 protein, potentially involved in immune checkpoints, were identified for PTLDS. 

Source: bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-10238-x