Genome-wide Association Study of Multisite Chronic Pain in UK Biobank

Johnston, Keira J. A.; Adams, Mark; Nicholl, Barbara I; Strawbridge, Rona J.; Ferguson, Amy; McIntosh, Andrew M.; Bailey, Mark E.S.; Smith, Daniel J.

doi:10.1101/502807

Cited by 36 publications

(78 citation statements)

References 134 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another approach recently applied in GWAS of chronic pain is based on obtaining a phenotype of multisite chronic pain (MCP) as a sum of the number of anatomical sites affected by pain (a study by Johnston et al 66 ). Johnston et al carried out a large-scale GWAS of MCP in~380,000 UK Biobank participants.…”

Section: Discussionmentioning

confidence: 99%

Analysis of genetically independent phenotypes identifies shared genetic factors associated with chronic musculoskeletal pain conditions

et al. 2020

View full text Add to dashboard Cite

Chronic musculoskeletal pain affects all aspects of human life. However, mechanisms of its genetic control remain poorly understood. Genetic studies of pain are complicated by the high complexity and heterogeneity of pain phenotypes. Here, we apply principal component analysis to reduce phenotype heterogeneity of chronic musculoskeletal pain at four locations: the back, neck/shoulder, hip, and knee. Using matrices of genetic covariances, we constructed four genetically independent phenotypes (GIPs) with the leading GIP (GIP1) explaining 78.4% of the genetic variance of the analyzed conditions, and GIP2-4 explain progressively less. We identified and replicated five GIP1-associated loci and one GIP2associated locus and prioritized the most likely causal genes. For GIP1, we showed enrichment with multiple nervous system-related terms and genetic correlations with anthropometric, sociodemographic, psychiatric/personality traits and osteoarthritis. We suggest that GIP1 represents a biopsychological component of chronic musculoskeletal pain, related to physiological and psychological aspects and reflecting pain perception and processing.

show abstract

Section: Discussionmentioning

confidence: 99%

Analysis of genetically independent phenotypes identifies shared genetic factors associated with chronic musculoskeletal pain conditions

et al. 2020

View full text Add to dashboard Cite

show abstract

“…All of these regions have been previously implicated in the modulation of pain (43–46), and also concur with the tissue expression analysis (Figure 2, Figure 3) which suggests that the central nervous system modulates neck or shoulder pain. A recent GWAS study suggested that FOXP2 is a candidate gene for multisite chronic pain (47). Further studies into the location and function of the transcription targets of FOXP2 would also provide valuable insight.…”

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

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

“…Large sample size GWAS summary data on chronic pain and sleep disturbance were used to explore their genetic correlations. The GWAS summary data of chronic pain was from a multisite GWAS of chronic pain in the UK Biobank, which included~380,000 participants 11 . The PSQI is a widely used measure of sleep quality with high sensitivity (98.7%) and specificity (84.4%) 40 for identifying primary insomnia 33,41,42 .…”

Section: Gwas Summary Statistics Data Of Chronic Pain and Sleep Distumentioning

confidence: 99%

Polygenic evidence and overlapped brain functional connectivities for the association between chronic pain and sleep disturbance

et al. 2020

View full text Add to dashboard Cite

Chronic pain and sleep disturbance are highly comorbid disorders, which leads to barriers to treatment and significant healthcare costs. Understanding the underlying genetic and neural mechanisms of the interplay between sleep disturbance and chronic pain is likely to lead to better treatment. In this study, we combined 1206 participants with phenotype data, resting-state functional magnetic resonance imaging (rfMRI) data and genotype data from the Human Connectome Project and two large sample size genome-wide association studies (GWASs) summary data from published studies to identify the genetic and neural bases for the association between pain and sleep disturbance. Pittsburgh sleep quality index (PSQI) score was used for sleep disturbance, pain intensity was measured by Pain Intensity Survey. The result showed chronic pain was significantly correlated with sleep disturbance (r = 0.171, p-value < 0.001). Their genetic correlation was r g = 0.598 using linkage disequilibrium (LD) score regression analysis. Polygenic score (PGS) association analysis showed PGS of chronic pain was significantly associated with sleep and vice versa. Nine shared functional connectivity (FCs) were identified involving prefrontal cortex, temporal cortex, precentral/ postcentral cortex, anterior cingulate cortex, fusiform gyrus and hippocampus. All these FCs mediated the effect of sleep disturbance on pain and seven FCs mediated the effect of pain on sleep disturbance. The chronic pain PGS was positively associated with the FC between middle temporal gyrus and hippocampus, which further mediated the effect of chronic pain PGS on PSQI score. Mendelian randomization analysis implied a possible causal relationship from chronic pain to sleep disturbance was stronger than that of sleep disturbance to chronic pain. The results provided genetic and neural evidence for the association between pain and sleep disturbance, which may inform future treatment approaches for comorbid chronic pain states and sleep disturbance.

show abstract

Genome-wide Association Study of Multisite Chronic Pain in UK Biobank

Cited by 36 publications

References 134 publications

Analysis of genetically independent phenotypes identifies shared genetic factors associated with chronic musculoskeletal pain conditions

Analysis of genetically independent phenotypes identifies shared genetic factors associated with chronic musculoskeletal pain conditions

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

Polygenic evidence and overlapped brain functional connectivities for the association between chronic pain and sleep disturbance

Contact Info

Product

Resources

About