A genome-wide association study finds genetic variants associated with neck or shoulder pain in UK Biobank

BackgroundCommon types of musculoskeletal conditions include pain in the neck and shoulder areas. This study seeks to identify the genetic variants associated with neck or shoulder pain based on a genome-wide association approach using 203,309 subjects from the UK Biobank cohort and look for replication evidence from the Generation Scotland: Scottish Family Health Study (GS:SFHS) and TwinsUK.MethodsCases in the UK Biobank were determined by a question which asked the participants if they had experienced pain in the neck or shoulder in the previous month influencing daily activities. Controls were the UK Biobank participants who reported no pain anywhere in the last month. A genome-wide association study was performed adjusting for age, sex, BMI and 9 population principal components. Significant and independent genetic variants were then sent to GS:SFHS and TwinsUK for replication.ResultsWe identified 3 genetic loci that were associated with neck or shoulder pain in the UK Biobank samples. The most significant locus was in an intergenic region in chromosome 17, rs12453010, havingP= 1.66 × 10-11. The second most significant locus was located in theFOXP2gene in chromosome 7 withP= 2.38 × 10-10for rs34291892. The third locus was located in theLINC01572gene in chromosome 16 withP= 4.50 × 10-8for rs62053992. In the replication stage, among 4 significant and independent genetic variants, rs2049604 in theFOXP2gene and rs62053992 in theLINC01572gene were weakly replicated in GS:SFHS (P =0.0240 andP= 0.0202, respectively). None of the single nucleotide polymorphisms (SNPs) were replicated in the TwinsUK cohort (P> 0.05).ConclusionsWe have identified 3 loci associated with neck or shoulder pain in the UK Biobank cohort, two of which were weakly supported in a replication cohort. Further evidence is needed to confirm their roles in neck or shoulder pain.SignificanceThis is the first genome-wide association study on neck or shoulder pain. We have identified 3 genetic loci (an intergenic region in chromosome 17, theFOXP2gene in chromosome 7, and theLINC01572gene in chromosome 16) that are associated with neck or shoulder pain using the UK Biobank cohort, among which theFOXP2gene and theLINC01572gene were weakly replicated by the Generation Scotland: Scottish Family Health Study (P< 0.05). The SNP heritability was 0.11, indicating neck or shoulder pain is a heritable trait. The tissue expression analysis suggested that neck or shoulder pain was related to multiple brain tissues, indicating the involvement of neuron function. The results will inform further research in the characterisation of the mechanisms of neck or shoulder pain.