Initial findings from the DecodeME genome-wide association study of myalgic encephalomyelitis/chronic fatigue syndrome

作者：Genetics Delivery Team, Thibaud Boutin, Andrew D. Bretherick, Joshua J Dibble, Esther Oluwada Ewaoluwagbemiga, Emma Northwood, Gemma L. Samms, Véronique 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 Wilson, Marketing and Communications Team, Helen C. Baxter, Danielle Boobyer, Claire Dransfield, Daphne Lamirel, Isabel Lewis, Nina Muirhead, Ella Ponting, Charles Shepherd, Alice Turner, Sumy V. Baby, Sjoerd Viktor Beentjes, John Ireland, Ava Khamseh, Ewan McDowall, David Perry, Joshua Slaughter, Erik Abner, Cindy G. Boer, Sarah Finer, Hele Haapaniemi, Hanna M. Ollila, Beth Pollack, Judith G.M. 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 · 发表于：medRxiv · 年份：2025 · DOI：10.1101/2025.08.06.25333109 · 被引用次数：5 · 研究领域：Fibromyalgia and Chronic Fatigue Syndrome Research、Genetic Neurodegenerative Diseases、T-cell and Retrovirus Studies

ABSTRACT Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) is a common, poorly understood disease that has no effective treatments, and has long been underserved by scientific research and national health systems. It is a sex-biased disease towards females that is often triggered by an infection, and its hallmark symptom is post-exertional malaise. People with ME/CFS often report their symptoms being disbelieved. The biological mechanisms causing ME/CFS remain unclear. We recruited 21,620 ME/CFS cases and performed genome-wide association studies (GWAS) for up to 15,579 cases and 259,909 population controls with European genetic ancestry. In these GWAS, we discovered eight loci that are significantly associated with ME/CFS, including three near BTN2A2, OLFM4 , and RABGAP1L genes that act in the response to viral or bacterial infection. Four of the eight loci ( RABGAP1L, FBXL4, OLFM4, CA10 ) were associated at p < 0.05 with cases ascertained using post-exertional malaise and fatigue in the UK Biobank and the Netherlands biobank Lifelines. We found no evidence of sex-bias among discovered associations, and replicated in males two genetic signals ( ARFGEF2, CA10 ) discovered in females. The ME/CFS association near CA10 colocalises with a known association to multisite chronic pain. We found no evidence that the eight ME/CFS genetic signals share common causal genetic variants with depression or anxiety. Our findings suggest that both immunological and neurological pr...