Genetic impact of blood C-reactive protein levels on chronic spinal & widespread pain

Autor: Scott F. Farrell, Michele Sterling, David M. Klyne, Sanam Mustafa, Adrián I. Campos, Pik-Fang Kho, Mischa Lundberg, Miguel E. Rentería, Trung Thanh Ngo, Gabriel Cuéllar-Partida
Rok vydání: 2023
Předmět:
Zdroj: European Spine Journal.
ISSN: 1432-0932
0940-6719
DOI: 10.1007/s00586-023-07711-7
Popis: Purpose 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. Methods 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 Results 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). Conclusion 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.
Databáze: OpenAIRE
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