Genetic impact of blood C-reactive protein levels on chronic spinal & widespread pain.
C-reactive protein
Chronic pain
Genetic predisposition to disease
Genome-wide association study
Inflammation biomarkers
Musculoskeletal pain
Journal
European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society
ISSN: 1432-0932
Titre abrégé: Eur Spine J
Pays: Germany
ID NLM: 9301980
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
received:
15
10
2022
accepted:
06
04
2023
revised:
27
02
2023
medline:
5
6
2023
pubmed:
18
4
2023
entrez:
17
4
2023
Statut:
ppublish
Résumé
Causal mechanisms underlying systemic inflammation in spinal & widespread pain remain an intractable experimental challenge. Here we examined whether: (i) associations between blood C-reactive protein (CRP) and chronic back, neck/shoulder & widespread pain can be explained by shared underlying genetic variants; and (ii) higher CRP levels causally contribute to these conditions. Using genome-wide association studies (GWAS) of chronic back, neck/shoulder & widespread pain (N = 6063-79,089 cases; N = 239,125 controls) and GWAS summary statistics for blood CRP (Pan-UK Biobank N = 400,094 & PAGE consortium N = 28,520), we employed cross-trait bivariate linkage disequilibrium score regression to determine genetic correlations (rG) between these chronic pain phenotypes and CRP levels (FDR < 5%). Latent causal variable (LCV) and generalised summary data-based Mendelian randomisation (GSMR) analyses examined putative causal associations between chronic pain & CRP (FDR < 5%). Higher CRP levels were genetically correlated with chronic back, neck/shoulder & widespread pain (rG range 0.26-0.36; P ≤ 8.07E-9; 3/6 trait pairs). Although genetic causal proportions (GCP) did not explain this finding (GCP range - 0.32-0.08; P ≥ 0.02), GSMR demonstrated putative causal effects of higher CRP levels contributing to each pain type (beta range 0.027-0.166; P ≤ 9.82E-03; 3 trait pairs) as well as neck/shoulder pain effects on CRP levels (beta [S.E.] 0.030 [0.021]; P = 6.97E-04). This genetic evidence for higher CRP levels in chronic spinal (back, neck/shoulder) & widespread pain warrants further large-scale multimodal & prospective longitudinal studies to accelerate the identification of novel translational targets and more effective therapeutic strategies.
Identifiants
pubmed: 37069442
doi: 10.1007/s00586-023-07711-7
pii: 10.1007/s00586-023-07711-7
doi:
Substances chimiques
C-Reactive Protein
9007-41-4
CRP protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2078-2085Informations de copyright
© 2023. The Author(s).
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