Chronic widespread musculoskeletal pain (CWP) is a symptom of fibromyalgia and a complex trait with poorly understood pathogenesis. CWP is heritable (48%-54%), but its genetic architecture is unknown and candidate gene studies have produced inconsistent results. We conducted a genome-wide association study to get insight into the genetic background of CWP.
Northern Europeans from UK Biobank comprising 6914 cases reporting pain all over the body lasting >3 months and 242 929 controls were studied. Replication of three independent genome-wide significant single nucleotide polymorphisms was attempted in six independent European cohorts (n=43 080; cases=14 177). Genetic correlations with risk factors, tissue specificity and colocalisation were examined.
Three genome-wide significant loci were identified () residing within the genes (), () and (). The locus was replicated (meta-analysis p=0.0002), the locus showed suggestive association (p=0.0227) and the locus was not replicated. Partial genetic correlation between CWP and depressive symptoms, body mass index, age of first birth and years of schooling were identified. Tissue specificity and colocalisation analysis highlight the relevance of skeletal muscle in CWP.
We report a novel association of locus and a suggestive association of locus with CWP. Both loci are consistent with a role of calcium regulation in CWP. The association with , one of the most studied genes in chronic pain field, was not confirmed in the replication analysis.

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