Genetic correlations between pain phenotypes and depression and neuroticism

Wang, Meng; Adams, Mark J.; Reel, Parminder Singh; Rajendrakumar, Aravind Lathika; Huang, Yu; Deary, Ian J.; Palmer, Colin N.A.; McIntosh, Andrew M.; Smith, Blair H.

doi:10.1038/s41431-019-0530-2

Cited by 61 publications

(55 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The SNP heritability of neck or shoulder pain was 0.11. This is similar to that of back pain (0.11), greater than knee pain (0.08), and less than: hip pain (0.12), stomach or abdominal pain (0.14), headache (0.21), facial pain (0.24), and pain all over the body (0.31) (51). Further, the genetic correlation matrix among 8 pain phenotypes in the UK Biobank showed that the neck or shoulder pain and back pain shared the highest genetic correlation (rg = 0.83) (51).…”

Section: Discussionsupporting

confidence: 69%

“…The genetic correlation analysis results were perhaps to be expected. Like knee pain and back pain, which have been shown to be positively correlated with depression and neuroticism (51), neck or shoulder pain was correlated genetically and positively with some mental health and personality phenotypes. We also identified that neck or shoulder pain was genetically and negatively correlated with the age at which they have their first child, college completion, and years of schooling.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Wang¹,

Chan²,

Harris³

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

ABSTRACTBackgroundCommon 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, 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 4 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). 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, the FOXP2 gene in chromosome 7, and the LINC01572 gene in chromosome 16) that are associated with neck or shoulder pain using the UK Biobank cohort, among which the FOXP2 gene and the LINC01572 gene 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.

show abstract

Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

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

Wang¹,

Chan²,

Harris³

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Further, precision medicine approaches need such a better understanding of the precise relationship between genes and phenotype to reveal underlying biological mechanisms. Finally, the discovery of novel subclasses may eventually translate into clinical care [24]. Recent studies have shown progress in the genetic correlations between pain phenotypes and psychiatric traits or using RNA sequence analysis on chondrocytes from osteoarthritis patients [25].…”

Section: Introductionmentioning

confidence: 99%

Validity of the cold pressor test and pain sensitivity questionnaire via online self-administration

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Also, we used common SNPs to estimate the heritability of CWP, so the contribution of other variants in the heritability estimated remains unknown. Other musculoskeletal pain assessed in UKB (knee, hip, back, and neck or shoulder pain) exhibited SNP-heritability on the liability scale in the range 0.08–0.12[62], and these estimates are considerably lower than our estimate for CWP, suggesting CWP is a trait of high genetic influence.…”

Section: Discussionmentioning

confidence: 67%

“…Second, we observed a tendency towards non-significance for the COMT locus in the sensitivity GWAS due to the exclusion of participants with non-musculoskeletal pain from the control group suggesting that COMT predisposes to chronic pain in general. 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 .…”

Section: Discussionmentioning

confidence: 99%

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

Rahman

Winsvold

Chavez

et al. 2020

Preprint

View full text Add to dashboard Cite

Background and Objectives: 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. Methods: Northern Europeans from UK Biobank comprising 6,914 cases reporting pain all over the body lasting more than 3 months and 242,929 controls were studied. Replication of three lead genome-wide significant single nucleotide polymorphisms (SNPs) was attempted in 6 independent European cohorts (N=43,080; cases=14,177). Genetic correlations with risk factors, tissue specificity, and colocalization were examined. Results: Three genome-wide significant loci were identified (rs1491985, rs10490825, rs165599) residing within the genes RNF123, ATP2C1, and COMT. The RNF123 locus was replicated (meta-analysis p=0.0002), the ATP2C1 locus showed suggestive association (p=0.0227), and the COMT 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 colocalization analysis highlight the relevance of skeletal muscle in CWP. Conclusions: We report a novel association of RNF123 locus with CWP and suggest a role of ATP2C1, consistent with a role of calcium regulation in CWP. The association to COMT, one of the most studied genes in chronic pain field, was not confirmed in the replication analysis.

show abstract

Genetic correlations between pain phenotypes and depression and neuroticism

Cited by 61 publications

References 47 publications

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

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

Validity of the cold pressor test and pain sensitivity questionnaire via online self-administration

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

Contact Info

Product

Resources

About