The Genetics of Fibromyalgia and its Relationships to Psychiatric and Medical Traits

Fibromyalgia is a chronic heritable syndrome, with little prior genetic work taking a syndromic approach. In this study we aimed to discover genetic mechanisms underlying fibromyalgia. We conducted genome-wide association studies (GWAS) of fibromyalgia in subjects of European (EUR), African (AFR) and Latin American (AMR) ancestries, combining data from several samples (total N, 85,139 cases; 1,642,433 controls). We also conducted a multi-trait analysis of GWAS (MTAG), leveraging pain summary statistics to achieve enhanced power for fibromyalgia analyses. We then applied a series of post-GWAS methods to analyze the genetic association between fibromyalgia and a variety of psychological and physiological phenotypes. We found 10 genome-wide significant (GWS) loci associated with fibromyalgia in EUR, 1 in AFR, 12 cross-ancestry, and 45 in the EUR MTAG. Most of these loci were previously associated with pain, cognitive function, autoimmune response, or general health measures like BMI and blood pressure. Genetic correlation analysis revealed a moderate negative correlation with physical activity, and strong genetic correlations with chronic pain, PTSD and depression (rg [≥] 0.69). Genomic structural equation modeling helped to place fibromyalgia in the context of a set of psychiatric, medical, and lifestyle traits. Additional findings regarding local genetic correlations and genetic causality point to genetic 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.