A massive study unveils the genetic underpinnings of fibromyalgia

The mysterious pain disorder fibromyalgia may have some surprising genetic roots.

An analysis of 2.5 million people suggests fibromyalgia is neurological in nature, scientists report July 28 in Nature Medicine. The genetics study is the latest — and largest — to try and get a grasp on a long-debated condition.

The work establishes a biological basis for fibromyalgia, which was historically thought to be psychological. Evidence of the condition’s biological origins has been accumulating for years, says Michael Wainberg, a geneticist at the University of Toronto. “But now,” he says, “I think it’s absolutely indisputable.”

Fibromyalgia is known for causing widespread pain and fatigue, though symptoms can look different among patients. They may also have anxiety, depression and sleep disruptions, says Jonathan Aebischer, a chronic pain researcher and clinician at Oregon Health & Science University in Portland who was not part of the new study. “I can’t say that I’ve ever seen two cases of fibromyalgia that are exactly alike,” he says. 

And though fibromyalgia has real, physical symptoms, they can appear to be invisible, says Kristal Kent, a patient advocate at the nonprofit organization Veteran Voices for Fibromyalgia, based in Cleveland. “One day, I can seem OK,” she says, “and the next day I could be crashed out in a flare-up.” For her, some of the biggest symptoms are chronic fatigue and brain fog.

Fibromyalgia affects some 4 million adults in the United States, but the true number of people affected might be even higher, says Hanna Ollila, a genetic epidemiologist at the University of Helsinki. Besides the symptom variability, there are no blood tests to screen for fibromyalgia and it can be misdiagnosed as other diseases. What’s more, “there are still to this day physicians who don’t really believe it’s a real condition,” says Gerard Limerick, a pain medicine doctor at Johns Hopkins School of Medicine who was not involved with the work. Among those who accept the condition as real, there’s debate about fibromyalgia’s origins. Some evidence has suggested the condition is an autoimmune one.

But scientists don’t have a good understanding of what drives the disorder. They know genetics factor in because fibromyalgia can run in families. Yet no one had pinned down what parts of people’s genetic instruction books might be involved. Ollila, Wainberg and their colleagues uncovered 26 regions of the genome that might enhance people’s risk.

The team analyzed the genomes of 2.5 million people, nearly 55,000 of whom had been diagnosed with fibromyalgia. The researchers were looking for genetic variants that occurred in people with the disorder more or less often than in the general population. Such variants offer clues about fibromyalgia’s biology.

Of the 26 fibromyalgia-linked variants uncovered, about half occurred near genes with neural roles, like regulating nerve cell growth and controlling pain sensitivity. But the variant most strongly linked to fibromyalgia appeared in a gene no one expected — the gene responsible for Huntington’s disease. “It’s extremely surprising,” Wainberg says.

Huntington’s is a fatal neurodegenerative disease that can cause debilitating problems with movement, including walking, talking and swallowing. Until now, no one had reported any such link between Huntington’s and fibromyalgia. But that doesn’t mean people with one disease are at risk of developing the other, Wainberg says. The mutation responsible for Huntington’s is not the same as the one found in people with fibromyalgia, the team reported. The researchers do not yet know what role — if any — the new variant plays in fibromyalgia. 

The study suggests a primarily neurological basis for fibromyalgia, “but that doesn’t mean other things don’t matter as well,” says Nasa Sinnott-Armstrong, a statistical geneticist at Fred Hutchinson Cancer Center in Seattle. The immune system may still be important in the development of this disease.

Kent thinks the new study might drive more productive conversations between patients and providers. Perhaps the medical community will take fibromyalgia more seriously now, she says.

Though the new work reveals fibromyalgia’s genetic underpinnings, the variants discovered aren’t the kind of disease indicators that doctors can use for diagnosis, Olilla says. And the dataset the team examined did not represent people of all ancestries. But the information could help uncover new therapeutic paths.

Think about the genetic variants like a plume of smoke drifting up somewhere in your neighborhood, Limerick says. It tells firefighters where to look but doesn’t give an exact location. Similarly, the variants don’t tell researchers the exact cause of fibromyalgia, but they “point you in a direction to investigate further.”