Researchers Find Genetic Variants That Increase Risk of Fibromyalgia
/By Pat Anson
The origins and causes of fibromyalgia have long baffled patients, doctors and researchers. Over the years, fibromylagia has been blamed on everything from gut bacteria and childhood trauma to a brain disorder and weakened immune system.
Through it all, fibromyalgia remains a poorly understood disorder characterized by deep tissue pain, headaches, fatigue, anxiety, depression and insomnia. Nearly 3% of the world’s population has fibromyalgia, with females making up 75% of cases
An international team of researchers has now identified over two dozen genetic variants that play a role in the development of fibromyalgia. Their findings, published in Nature Medicine, suggest the nervous system plays an important causal role.
The team analyzed genetic data from more than 2.5 million adults around the world, including 55,000 who had been diagnosed with fibromyalgia. Researchers looked for genetic differences in people with and without fibromyalgia to find the genes that were most common in those with the condition.
This helped them identify genetic variants in 26 regions of the DNA genome that appear to play a role in fibromyalgia’s development. Many of the genes implicated in these regions are involved in brain and nerve function, and are associated with fibromyalgia’s physical and psychiatric traits.
"This work changes how we think about fibromyalgia at a fundamental level. For decades, patients have been dismissed or told their pain is simply psychological. Our findings confirm the condition has a clear biological basis," said co-senior author Michael Wainberg, PhD, an investigator at the Lunenfeld-Tanenbaum Research Institute and Assistant Professor of Psychiatry at the University of Toronto.
Of the 26 genetic variants identified, the one most strongly linked to fibromyalgia risk was within the gene HTT. Different mutations in the HTT gene cause Huntington's disease, a severe, progressive and fatal neurodegenerative disorder.
Further genetic analysis revealed moderate-to-strong positive associations between fibromyalgia and several psychiatric disorders, namely depression, suicidality, ADHD and PTSD. These correlations help explain the high comorbidity between fibromyalgia and these emotional states.
The study also revealed substantial genetic overlap between fibromyalgia and a range of painful conditions, including low back pain, migraine and irritable bowel syndrome. The researchers think shared biological mechanisms within the nervous system may make people susceptible to several of these conditions, explaining why they often appear together.
"We know that chronic pain syndromes cluster together in individuals and families and are genetically similar. Targeting the shared mechanisms underlying them could potentially benefit a whole cluster of disorders," said co-senior author Frances Williams, PhD, Professor of Genomic Epidemiology at King's College London.
"The findings also help us better understand why fibromyalgia so often occurs alongside conditions such as anxiety and depression, bringing us closer to understanding the condition as a whole."
Genetics alone do not determine whether someone develops fibromyalgia. Researchers suspect that even people who carry many of fibromyalgia’s genetic variants require other risk factors, such as arthritis, to trigger fibromyalgia.
"This study provides important new insights into why some people develop fibromyalgia syndrome and identifies biological pathways that could lead to new treatment approaches. One of these pathways is already the focus of drug trials for Huntington's disease, raising the possibility that existing pharmaceutical research could eventually benefit people with fibromyalgia,” said Williams.
Williams and her colleagues have founded the Chronic Pain Genomics Consortium to investigate other chronic pain syndromes, starting with pelvic pain. The consortium sees fibromyalgia as only the beginning of a broader exploration of the landscape of chronic pain conditions.
