The genetics of fibromyalgia and its relationships to psychiatric and medical traits.

We explore the genetic mechanisms underlying fibromyalgia, a chronic heritable syndrome. We conduct genome-wide association studies (GWAS) of fibromyalgia in European, African, and Latin American ancestry subjects, combining data from several cohorts (85,139 cases; 1,642,433 controls). We also conduct a multi-trait analysis of GWAS (MTAG), leveraging pain GWAS to enhance power for fibromyalgia analyses. We apply a series of methods to analyze genetic association between fibromyalgia and psychological and physiological phenotypes. We find 10 genomic loci that are associated with fibromyalgia in European ancestry subjects, one in African, 12 cross-ancestry, and 45 in the European ancestry MTAG; most of these were previously associated with pain, cognitive function, autoimmune response, or general health measures. We show a moderate negative genetic correlation between fibromyalgia and physical activity, and strong genetic correlations with chronic pain, post-traumatic stress disorder, and depression (rg≥0.69). Genomic structural equation modeling places fibromyalgia in the context of psychiatric, medical, and lifestyle phenotypes, mostly as pain- and autoimmune-related trait. Local genetic correlations and genetic causality point to neuronal mechanisms that provide a strong basis for some of the main characteristics of fibromyalgia and its comorbidities. These findings provide potential targets for future studies to improve diagnosis and treatment of fibromyalgia.