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Overview

Johnston et al. performed a genome-wide association study (GWAS) of Multisite Chronic Pain (MCP) using data from 387,649 UK Biobank participants. To quantify MCP, participants reported the number of body sites where they had experienced pain recently and for at least 3 months, with values ranging from 0 to 7. The study identified 76 independent SNPs at 39 loci which were significantly associated with MCP.1

Notably, the DecodeME study found that ME/CFS colocalized with MCP near the gene that encodes carbonic anhydrase-related protein 10 (CA10). This locus on chromosome 17 was also found to colocalize with a variant which is associated with increased expression of CA10 in the prostate.2 CA10 is most highly expressed in tissues of the central nervous system.34 Research suggests that CA10 localizes to neural synapses and binds to neurexins, which are proteins involved in synaptogenesis.5 These links between CA10 and the nervous system align with other findings which suggest nervous system involvement in both chronic pain and ME/CFS, such as significant MAGMA brain tissue enrichment in both of the above studies.12

Several studies have also noted a high rate of pain in individuals with ME/CFS.6 Consistent with previous research, the DecodeME study found that 86.1% of 16,730 ME/CFS cases reported experiencing muscle pain.2

To potentially gain further insights into both chronic pain and ME/CFS, the mecfs_bioinformatics repo was used to further analyze Johnston et al.'s MCP study.

To reproduce this analysis run the Multisite Chronic Pain GWAS Analysis Script.

  1. Keira JA Johnston, Mark J Adams, Barbara I Nicholl, Joey Ward, Rona J Strawbridge, Amy Ferguson, Andrew M McIntosh, Mark ES Bailey, and Daniel J Smith. Genome-wide association study of multisite chronic pain in UK Biobank. PLoS Genetics, 15(6):e1008164, 2019. URL: https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1008164. ↩↩

  2. Genetics Delivery Team, Thibaud Boutin, Andrew D Bretherick, Joshua J Dibble, Esther Ewaoluwagbemiga, Emma Northwood, Gemma L Samms, Veronique Vitart, Project, Cohort Delivery Team, Øyvind Almelid, and others. Initial findings from the DecodeME genome-wide association study of myalgic encephalomyelitis/chronic fatigue syndrome. medRxiv, pages 2025–08, 2025. URL: https://www.medrxiv.org/content/10.1101/2025.08.06.25333109v1. ↩↩↩

  3. Mathias Uhlén, Linn Fagerberg, Björn M Hallström, Cecilia Lindskog, Per Oksvold, Adil Mardinoglu, Åsa Sivertsson, Caroline Kampf, Evelina Sjöstedt, Anna Asplund, and others. Tissue-based map of the human proteome. Science, 347(6220):1260419, 2015. URL: https://www.science.org/doi/10.1126/science.1260419. ↩

  4. Tissue expression of CA10 - summary - The Human Protein Atlas. [Accessed 24-02-2026]. URL: https://www.proteinatlas.org/ENSG00000154975-CA10/tissue. ↩

  5. Fredrik H Sterky, Justin H Trotter, Sung-Jin Lee, Christian V Recktenwald, Xiao Du, Bo Zhou, Peng Zhou, Jochen Schwenk, Bernd Fakler, and Thomas C Südhof. Carbonic anhydrase-related protein CA10 is an evolutionarily conserved pan-neurexin ligand. Proceedings of the National Academy of Sciences, 114(7):E1253–E1262, 2017. URL: https://pnas.org/doi/full/10.1073/pnas.1621321114. ↩

  6. Board on the Health of Select Populations and Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Beyond myalgic encephalomyelitis/chronic fatigue syndrome: redefining an illness. National Academies Press, 2015. URL: https://www.ncbi.nlm.nih.gov/books/NBK274235/. ↩