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

Abstract

Background Common 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. Methods A genome-wide association study was performed adjusting for age, sex, BMI and nine population principal components. Significant and independent genetic variants were then sent to GS:SFHS and TwinsUK for replication. Results We identified three 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, having P = 1.66 × 10−11. The second most significant locus was located in the FOXP2 gene in chromosome 7 with P = 2.38 × 10−10 for rs34291892. The third locus was located in the LINC01572 gene in chromosome 16 with P = 4.50 × 10−8 for rs62053992. In the replication stage, among four significant and independent genetic variants, rs2049604 in the FOXP2 gene and rs62053992 in the LINC01572 gene were weakly replicated in GS:SFHS (P = 0.0240 and P = 0.0202, respectively). Conclusions We have identified three 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.

Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain

“…Finally, genetic factors underlying chronic pain and psychiatric co-morbidity (e.g., depression and neuroticism) are known to be shared[62]. However, previous GWAS on chronic pain[29, 63, 64], depression[65] and neuroticism[66] have failed to detect an association with COMT . Thus, if there is a role of COMT in CWP, it is likely minimal.…”

“…However, previous GWAS on chronic pain [29,63,64], depression [65] and neuroticism [66] have failed to detect an association with COMT. Thus, if there is a role of COMT in CWP, it is likely minimal.…”

Genome-wide association study of pain sensitivity assessed by questionnaire and the cold pressor test

“…We used two self-administered pain sensitivity measurements, the PSQ and CPT, and established that they could be reliable phenotypes for evaluating the genetic architecture of pain sensitivity. PSQ score and CPT duration have been previously shown to be only moderately phenotypically correlated (r = -0.22 [-0.27, -0.17]) [8]. The PSQ is a pain intensity rating of imagined painful situations occurring in daily life, whereas the CPT directly measures pain tolerance.…”

“…To date, the number of genome-wide association studies (GWAS) on pain phenotypes is still very limited. The largest pain GWAS have been performed in the UK Biobank and 23andMe, Inc. cohorts for chronic pain [5] [6], knee pain [7], neck and shoulder pain [8], and migraine [9] [10]. These studies have identified dozens of putative causal genes, which are primarily expressed within brain tissues and have been implicated in neurogenesis, neuronal development, neural connectivity, and cell-cycle processes.…”

Genome-Wide Association Analysis Identified ANXA1 Associated with Shoulder Impingement Syndrome in UK Biobank Samples

“…The SIS impingent hypothesis postulated a pathophysiological mechanism, different shoulder joint structures producing mechanical conflicts ( Garving et al 2017 ). A Genome-wide Association Study (GWAS) was recently performed to identify the genetic variants associated with neck or shoulder pain in the UK Biobank cohort, and three genetic loci were identified associated with neck or shoulder pain, such as rs2049604 in FOXP2 gene and rs62053992 in LINC01572 gene ( Meng et al 2020 ). However, the molecular mechanisms of SIS are rarely studied and the genetic pathogenesis of SIS is still unclear.…”