Large candidate gene association study reveals genetic risk factors and therapeutic targets for fibromyalgia

Objective Fibromyalgia (FM) represents a complex disorder that is characterized by widespread pain and tenderness and is frequently accompanied by additional somatic and cognitive/affective symptoms. Genetic risk factors are known to contribute to the etiology of the syndrome. The aim of this study was to examine >350 genes for association with FM, using a large-scale candidate gene approach. Methods. The study group comprised 496 patients with FM (cases) and 348 individuals with no chronic pain (controls). Genotyping was performed using a dedicated gene array chip, the Pain Research Panel, which assays variants characterizing >350 genes known to be involved in the biologic pathways relevant to nociception, inflammation, and mood. Association testing was performed using logistic regression. Results. Significant differences in allele frequencies between cases and controls were observed for 3 genes: GABRB3 (rs4906902; P = 3.65 x 10(-6)), TAAR1 (rs8192619; P = 1.11 x 10(-5)), and GBP1 (rs7911; P = 1.06 x 10(-4)). These 3 genes and 7 other genes with suggestive evidence for association were examined in a second, independent cohort of patients with FM and control subjects who were genotyped using the Perlegen 600K platform. Evidence of association in the replication cohort was observed for TAAR1, RGS4, CNR1, and GRIA4. Conclusion. Variation in these 4 replicated genes may serve as a basis for development of new diagnostic approaches, and the products of these genes may contribute to the pathophysiology of FM and represent potential targets for therapeutic action.