Et preprint af artiklen (1):
fastslår, at fibromyalgi er en sygdom i centralnervesystemet. Citat:
"This work provides the first robust genetic evidence defining fibromyalgia as a central nervous system disorder, thereby establishing a biological framework for its complex pathophysiology and extensive clinical comorbidities."
Bemærk at cirka halvdelen af de forskere, der har bidraget til artiklen er fra Danmark eller Island.
Forskerne afslørede variationer i 26 områder af DNAet fra fibromyalgi patienter. De involverede gener fremgår af tabel 1 i artiklen (1):Den primære analyse er vist i figur 2 fra artiklen (1):
"Additionally, certain risk loci overlapped with long COVID120 (BPTF) and ME/CFS (OLFM4, RABGAP1L/GPR52), two poorly characterized disorders, albeit with different lead variants. These findings could point towards genetic factors associated with comorbidities and/or clinically misdiagnosed conditions. However, another plausible explanation of this widespread pleiotropy is that fibromyalgia genetics capture a core, transdiagnostic vulnerability. Such shared genetic architecture, rooted in central nervous system function, could predispose individuals to a spectrum of conditions characterized by sensory and/or affective dysregulation, which may manifest clinically as fibromyalgia, irritable bowel syndrome, post-traumatic stress disorder, or a constellation of other disorders, depending on other genetic and environmental factors."
"Fibromyalgia is frequently comorbid with variety of disorders including pain conditions, irritable bowel syndrome, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), autoimmune disorders such as rheumatoid arthritis and systemic lupus erythematosus, neuropsychiatric traits such as depression and anxiety, and metabolic syndrome."
"Fibromyalgia is considered the prototypical central sensitization or nociplastic pain syndrome."
Og relationen til neuroinflammation nævnes. Citat:
"Central sensitization has been shown to reflect specific underlying biological processes, including neuroinflammation and glial activation (particularly in the dorsal horn of the spinal cord), altered functional connectivity according to magnetic resonance imagin, altered neurotransmitter levels, and altered neuronal electrophysiology. "
I relation til central sensitization / hypersensitivitet er genet CELF4 spændende. Om dette gen skriver fibromyalgi forskerne. Citat:
"Several associations implicated pathways relevant to pain processing. One notable finding involved rs11664242, an intergenic variant ~30 kilobases upstream of its nearest coding gene CELF4. CELF4 is an RNA-binding protein and translational regulator predominantly expressed in excitatory neurons, regulating synaptogenesis during neurodevelopment by exerting broad-spectrum effects on the translation of mRNAs with synaptic roles. CELF4 reduces pain and sensory sensitivity by negatively regulating nociceptor excitability, and CELF4 gene therapy is being explored as a therapeutic strategy for chronic pain."
CELF4 DNA variationer blev ikke påvist i det store DecodeME projetk med ME patienter, men CELF4 dukkede op i et andet minder genetisk studie af ME patienter. Det fremgår af tabel 1 i reference 3:
"These studies reveal that the translational regulator CELF4 is a powerful negative regulator of sensory neuron excitability and sensory thresholds to heat and mechanical stimuli resulting in thermal and mechanical hypersensitivity in uninjured mice and exacerbating hypersensitivity in injured mice."
Jeg synes, at det er værd at kigge nærmere på CELF4 og central sensitization / hypersensitivitet. En del patienter med fibromyalgi eller Myalgisk encephalomyelitis udvikler Multiple Chemical Sensitivity (MCS) og/eller Electro Magnetic Hypersensitivity (EHS). Kan der være en sammenhæng til DNA variationer i genet CELF4?
Referencer:
1) The genetic architecture of fibromyalgia across 2.5 million individuals
Isabel Kerrebijn, Gyda Bjornsdottir, Keon Arbabi, Lea Urpa, Hele Haapaniemi, Gudmar Thorleifsson, Lilja Stefansdottir, Stephan Frangakis, Jesse Valliere, Lovemore Kunorozva, Erik Abner, Caleb Ji, Bitten Aagaard, Henning Bliddal, Søren Brunak, Mie T Bruun, Maria Didriksen, Christian Erikstrup, Arni J Geirsson, Daniel F Gudbjartsson, Thomas F Hansen, Ingileif Jonsdottir, Stacey Knight, Kirk U Knowlton, Christina Mikkelsen, Lincoln D Nadauld, Thorunn A Olafsdottir, Sisse R Ostrowski, Ole BV Pedersen, Saedis Saevarsdottir, Astros T Skuladottir, Erik Sørensen, Hreinn Stefansson, Patrick Sulem, Olafur A Sveinsson, Gudny E Thorlacius, Unnur Thorsteinsdottir, Henrik Ullum, Arnor Vikingsson, Thomas M Werge, Chronic Pain Genomics Consortium, FinnGen, DBDS Genomic Consortium, Estonian Biobank Research Team, Genes & Health Research Team, Richa Saxena, Kari Stefansson, Chad M Brummett, Bente Glintborg, Daniel J Clauw, Thorgeir E Thorgeirsson, Frances MK Williams, Nasa Sinnott-Armstrong, Hanna M Ollila, Michael Wainberg
medRxiv 2025.09.18.25335914; doi: https://doi.org/10.1101/2025.09.18.25335914
https://www.medrxiv.org/content/10.1101/2025.09.18.25335914v1
This article is a preprint and has not been peer-reviewed [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.
2) Initial findings from the DecodeME genome-wide association study of myalgic encephalomyelitis/chronic fatigue syndrome
https://www.medrxiv.org/content/10.1101/2025.08.06.25333109v1
Genetics Delivery Team, Thibaud Boutin, Andrew D. Bretherick, Joshua J. Dibble, Esther Ewaoluwagbemiga, Emma Northwood, Gemma L. Samms, Veronique Vitart, Project and Cohort Delivery Team, Øyvind Almelid, Tom Baker, Malgorzata Clyde, Anne Connolly, Diana Garcia, Shona M. Kerr, Claire Tripp, Jareth C. Wolfe, Patient and Public Involvement, Jackie Goold, Gemma Hoyes, Sian Leary, Simon J. McGrath, Julie Milton, Anna Redshaw, Jim M. Wilson, Marketing and Communications Team, Helen Baxter, Danielle Boobyer, Claire Dransfield, Daphne Lamirel, Isabel Lewis, Nina Muirhead, Ella Ponting, Charles Shepherd, Alice Turner, University of Edinburgh Team, Sumy V. Baby, Sjoerd Beentjes, John Ireland, Ava Khamseh, Ewan McDowall, David Perry, Joshua Slaughter, Genetic Epidemiology of ME/CFS Consortium, Erik Abner, Cindy G. Boer, Estonian Biobank Research Team, Sarah Finer, Genes & Health Research Team, Hele Haapaniemi, Hanna M. Ollila, Beth Pollack, Judith Rosmalen, Erika Romppanen, Sirine Saafi, Richa Saxena, Nasa Sinnott-Armstrong, Anniina Tervi, Lea Urpa, Jesse Valliere, David A. van Heel, Management Team, Sonya Chowdhury, Andy Devereux-Cooke, Chris P. Ponting
medRxiv 2025.08.06.25333109; doi: https://doi.org/10.1101/2025.08.06.25333109
This article is a preprint and has not been peer-reviewed [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.
https://www.nature.com/articles/tp2015208
4) Mueth MG, Neufeld P, Michael M, McGrath-Conwell A, Grlickova-Duzevik E, King T, Straub C, Harrison BJ. The RNA-binding protein CELF4 is a negative regulator of sensory neuron excitability and mechanical and heat behavioral sensitivity. Neurobiol Pain. 2025 May 10;18:100184. doi: 10.1016/j.ynpai.2025.100184. PMID: 41089293; PMCID: PMC12516356.
https://pubmed.ncbi.nlm.nih.gov/41089293/
