For many years, people with fibromyalgia endured a double ordeal. They suffered from widespread pain, exhaustion, sleep disturbances, cognitive fog, and a variety of bodily symptoms, while at the same time facing disbelief from those around them and, on occasion, even from their physicians. Because routine tests revealed neither inflammation nor visible muscle damage, their pain was often regarded as vague, exaggerated, or ‘psychological.’
And yet fibromyalgia is not a rare disease. It is estimated to affect approximately 2–4% of the general population—millions of people worldwide—and is one of the most common conditions encountered in rheumatology, ranking, by some estimates, second only to osteoarthritis. An even larger proportion, about 10%, reports chronic widespread pain, although not everyone meets the full diagnostic criteria for fibromyalgia. In Greece, a conservative extrapolation of international prevalence rates suggests hundreds of thousands of potential sufferers, many of whom remain undiagnosed and spend years moving from one clinic and investigation to another. The resulting social and economic burden is immense. In our 1997 paper, we had already highlighted a prevalence of 1–4% for fibromyalgia and approximately 10% for chronic widespread pain, as well as the fact that pain and tenderness are distributed across the population as a continuum rather than as absolute, binary states.
A new, large-scale genetic study published in Nature Medicine (Kerrebijn, et al. 2026) now provides compelling evidence that fibromyalgia is a genuine disorder of the central nervous system. An analysis of genetic data from more than 2.5 million people of diverse ancestry identified 26 genomic loci associated with an increased risk of developing the condition. Many are linked to genes that regulate the function of the brain, neural cells, and the systems that process sensory information.
These findings also have a particular historical significance for me. In 1997, together with Daniel Clauw, I published an extensive paper in Neuroimmunomodulation entitled ‘Chronic Pain and Fatigue Syndromes: Overlapping Clinical and Neuroendocrine Features and Potential Pathogenic Mechanisms.’ At a time when the very existence of fibromyalgia was still being questioned, we proposed that the illness originated not primarily in the muscles or peripheral tissues, but in dysregulation of the central nervous system.
Our hypothesis, formulated 29 years ago, predicted that a genetic predisposition interacts with environmental factors and physical, psychological, or immune stressors, leading to chronic dysregulation of the human stress system. We suggested the involvement of the brain networks that process pain, the hypothalamic–pituitary–adrenal axes, the autonomic nervous system, and the descending pathways that normally inhibit pain. We also argued that many immune and peripheral alterations might be secondary consequences of this central dysregulation rather than the primary cause of the disease.
The new genetic study does not, of course, confirm every individual mechanism in that hypothesis. It does, however, strikingly validate its central core: genetic susceptibility, a neurobiological basis, and the primary involvement of the brain. The study did not reveal a genetic pattern pointing chiefly to an autoimmune disease. This does not exclude immune-system involvement in some patients, but it shifts the center of gravity from peripheral tissues to neural networks.
In fibromyalgia, therefore, the patient is not ‘imagining’ the pain. The brain generates and amplifies it through genuine biological mechanisms. Under normal circumstances, pain is a protective alarm system. Once central circuits become sensitized, however, the alarm continues to sound even when there is no ongoing injury. Normally painless stimuli acquire disproportionate intensity and duration. This is nociplastic pain: pain arising from altered signal processing rather than necessarily from inflammation, tissue injury, or damage to a peripheral nerve.
The dysregulation is not confined to pain. Many patients are hypersensitive to light, sound, odors, temperature, heartbeats, and signals arising from the internal organs. The brain has difficulty filtering and prioritizing this torrent of information. This helps explain why fibromyalgia so often coexists with migraine, irritable bowel syndrome, temporomandibular disorders, chronic low-back pain, chronic fatigue, and post-traumatic stress. We described this very family of overlapping syndromes in 1997 as potentially different expressions of a shared central vulnerability.
This picture is directly connected to the biology of chronic stress. The organism maintains stability through change—through allostasis—by mobilizing the brain, the autonomic nervous system, hormones, and immunity. When that mobilization becomes prolonged or disproportionate, adaptive allostasis may deteriorate into cacostasis. The protective system begins to inflict wear and tear: sleep, recovery, mood, cognitive function, and the physiological inhibition of pain are all disrupted.
Of particular interest is the finding that the genetic architecture is almost identical in women and men. As early as 1997, we had noted that the emphasis on so-called ‘tender points’ created a diagnostic bias toward women. Under modern criteria, fibromyalgia remains more common in women, but it also affects men to a substantial degree. The new study does not yet provide a diagnostic genetic test or a definitive cure. It does, however, open the way to precision medicine, the identification of biological subtypes, and the development of targeted drugs and neuromodulation techniques.
Its greatest achievement is at once scientific and ethical. It vindicates the lived experience of patients and reaffirms a principle that medicine must never forget: the absence of visible damage does not mean the absence of real disease. Fibromyalgia is not a disease ‘of the imagination,’ but a disorder arising from the complex biology of the brain, stress, and adaptation.
Commentary
On Kerrebijn, I., Bjornsdottir, G., Arbabi, K. et al. The genetic architecture of fibromyalgia across 2.5 million individuals. Nat Med 32, 3060–3070 (2026). DOI: https://www.nature.com/articles/s41591-026-04492-6
Author’s Affiliation
George P. Chrousos, MD, MACP, MACE, FRCP, ΣΞ, Professor of Pediatrics and Endocrinology Emeritus, Holder, UNESCO Chair on Adolescent Health Care, Director, University Research Institute of Maternal and Child Health and Precision Medicine, Medical School, National and Kapodistrian University of Athens, President, Hellenic Pasteur Institute, Athens, Greece
Fibromyalgia: A Scientific Prediction Confirmed 29 Years Later
For many years, people with fibromyalgia endured a double ordeal. They suffered from widespread pain, exhaustion, sleep disturbances, cognitive fog, and a variety of bodily symptoms, while at the same time facing disbelief from those around them and, on occasion, even from their physicians. Because routine tests revealed neither inflammation nor visible muscle damage, their pain was often regarded as vague, exaggerated, or ‘psychological.’
And yet fibromyalgia is not a rare disease. It is estimated to affect approximately 2–4% of the general population—millions of people worldwide—and is one of the most common conditions encountered in rheumatology, ranking, by some estimates, second only to osteoarthritis. An even larger proportion, about 10%, reports chronic widespread pain, although not everyone meets the full diagnostic criteria for fibromyalgia. In Greece, a conservative extrapolation of international prevalence rates suggests hundreds of thousands of potential sufferers, many of whom remain undiagnosed and spend years moving from one clinic and investigation to another. The resulting social and economic burden is immense. In our 1997 paper, we had already highlighted a prevalence of 1–4% for fibromyalgia and approximately 10% for chronic widespread pain, as well as the fact that pain and tenderness are distributed across the population as a continuum rather than as absolute, binary states.
A new, large-scale genetic study published in Nature Medicine (Kerrebijn, et al. 2026) now provides compelling evidence that fibromyalgia is a genuine disorder of the central nervous system. An analysis of genetic data from more than 2.5 million people of diverse ancestry identified 26 genomic loci associated with an increased risk of developing the condition. Many are linked to genes that regulate the function of the brain, neural cells, and the systems that process sensory information.
These findings also have a particular historical significance for me. In 1997, together with Daniel Clauw, I published an extensive paper in Neuroimmunomodulation entitled ‘Chronic Pain and Fatigue Syndromes: Overlapping Clinical and Neuroendocrine Features and Potential Pathogenic Mechanisms.’ At a time when the very existence of fibromyalgia was still being questioned, we proposed that the illness originated not primarily in the muscles or peripheral tissues, but in dysregulation of the central nervous system.
Our hypothesis, formulated 29 years ago, predicted that a genetic predisposition interacts with environmental factors and physical, psychological, or immune stressors, leading to chronic dysregulation of the human stress system. We suggested the involvement of the brain networks that process pain, the hypothalamic–pituitary–adrenal axes, the autonomic nervous system, and the descending pathways that normally inhibit pain. We also argued that many immune and peripheral alterations might be secondary consequences of this central dysregulation rather than the primary cause of the disease.
The new genetic study does not, of course, confirm every individual mechanism in that hypothesis. It does, however, strikingly validate its central core: genetic susceptibility, a neurobiological basis, and the primary involvement of the brain. The study did not reveal a genetic pattern pointing chiefly to an autoimmune disease. This does not exclude immune-system involvement in some patients, but it shifts the center of gravity from peripheral tissues to neural networks.
In fibromyalgia, therefore, the patient is not ‘imagining’ the pain. The brain generates and amplifies it through genuine biological mechanisms. Under normal circumstances, pain is a protective alarm system. Once central circuits become sensitized, however, the alarm continues to sound even when there is no ongoing injury. Normally painless stimuli acquire disproportionate intensity and duration. This is nociplastic pain: pain arising from altered signal processing rather than necessarily from inflammation, tissue injury, or damage to a peripheral nerve.
The dysregulation is not confined to pain. Many patients are hypersensitive to light, sound, odors, temperature, heartbeats, and signals arising from the internal organs. The brain has difficulty filtering and prioritizing this torrent of information. This helps explain why fibromyalgia so often coexists with migraine, irritable bowel syndrome, temporomandibular disorders, chronic low-back pain, chronic fatigue, and post-traumatic stress. We described this very family of overlapping syndromes in 1997 as potentially different expressions of a shared central vulnerability.
This picture is directly connected to the biology of chronic stress. The organism maintains stability through change—through allostasis—by mobilizing the brain, the autonomic nervous system, hormones, and immunity. When that mobilization becomes prolonged or disproportionate, adaptive allostasis may deteriorate into cacostasis. The protective system begins to inflict wear and tear: sleep, recovery, mood, cognitive function, and the physiological inhibition of pain are all disrupted.
Of particular interest is the finding that the genetic architecture is almost identical in women and men. As early as 1997, we had noted that the emphasis on so-called ‘tender points’ created a diagnostic bias toward women. Under modern criteria, fibromyalgia remains more common in women, but it also affects men to a substantial degree. The new study does not yet provide a diagnostic genetic test or a definitive cure. It does, however, open the way to precision medicine, the identification of biological subtypes, and the development of targeted drugs and neuromodulation techniques.
Its greatest achievement is at once scientific and ethical. It vindicates the lived experience of patients and reaffirms a principle that medicine must never forget: the absence of visible damage does not mean the absence of real disease. Fibromyalgia is not a disease ‘of the imagination,’ but a disorder arising from the complex biology of the brain, stress, and adaptation.
Commentary
On Kerrebijn, I., Bjornsdottir, G., Arbabi, K. et al. The genetic architecture of fibromyalgia across 2.5 million individuals. Nat Med 32, 3060–3070 (2026). DOI: https://www.nature.com/articles/s41591-026-04492-6
Author’s Affiliation
George P. Chrousos, MD, MACP, MACE, FRCP, ΣΞ, Professor of Pediatrics and Endocrinology Emeritus, Holder, UNESCO Chair on Adolescent Health Care, Director, University Research Institute of Maternal and Child Health and Precision Medicine, Medical School, National and Kapodistrian University of Athens, President, Hellenic Pasteur Institute, Athens, Greece