The genetic architecture of fibromyalgia across 2.5 million individuals.

Fibromyalgia is a common and debilitating chronic pain syndrome of poorly understood etiology. Here we conduct a multi-ancestry genome-wide association study meta-analysis across 2,563,755 individuals (54,629 cases and 2,509,126 controls) from 11 cohorts, identifying 26 risk loci for fibromyalgia. The strongest association was with a coding variant in HTT, the causal gene for Huntington's disease. Gene prioritization implicated the HTT regulator GPR52, as well as diverse genes with neural roles, including DCC, DRD2/NCAM1, MDGA2 and CELF4. Fibromyalgia heritability was exclusively enriched within brain tissues and neural cell types. Fibromyalgia showed strong, positive genetic correlation with a wide range of chronic pain, psychiatric and somatic disorders, including genetic correlations above 0.7 with low back pain, post-traumatic stress disorder and irritable bowel syndrome. Despite large sex differences in fibromyalgia prevalence, the genetic architecture of fibromyalgia was nearly identical between males and females. This study provides robust genetic evidence defining fibromyalgia as a central nervous system disorder, thereby establishing a biological framework for its complex pathophysiology and extensive clinical comorbidities.
Mental Health
Care/Management
Policy

Authors

Kerrebijn Kerrebijn, Bjornsdottir Bjornsdottir, Arbabi Arbabi, Urpa Urpa, Haapaniemi Haapaniemi, Thorleifsson Thorleifsson, Stefansdottir Stefansdottir, Frangakis Frangakis, Valliere Valliere, Kunorozva Kunorozva, Abner Abner, Ji Ji, Kangur Kangur, Aagaard Aagaard, Bliddal Bliddal, Brunak Brunak, Bruun Bruun, Didriksen Didriksen, Erikstrup Erikstrup, Finer Finer, Geirsson Geirsson, Gudbjartsson Gudbjartsson, Hansen Hansen, van Heel van Heel, Jonsdottir Jonsdottir, Knight Knight, Knowlton Knowlton, Mikkelsen Mikkelsen, Nadauld Nadauld, Olafsdottir Olafsdottir, Ostrowski Ostrowski, Pedersen Pedersen, Saevarsdottir Saevarsdottir, Skuladottir Skuladottir, Sørensen Sørensen, Stefansson Stefansson, Sulem Sulem, Sveinsson Sveinsson, Thorlacius Thorlacius, Thorsteinsdottir Thorsteinsdottir, Ullum Ullum, Vikingsson Vikingsson, Werge Werge, , , , , , Saxena Saxena, Stefansson Stefansson, Brummett Brummett, Glintborg Glintborg, Clauw Clauw, Thorgeirsson Thorgeirsson, Williams Williams, Sinnott-Armstrong Sinnott-Armstrong, Ollila Ollila, Wainberg Wainberg
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