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

Autor: Farrell SF; RECOVER Injury Research Centre, The University of Queensland, Level 7 STARS Hospital, 296 Herston Rd, Herston, QLD, 4029, Australia. Scott.Farrell@uq.edu.au.; NHMRC Centre of Research Excellence: Better Health Outcomes for Compensable Injury, The University of Queensland, Herston, QLD, Australia. Scott.Farrell@uq.edu.au.; Tess Cramond Pain & Research Centre, Royal Brisbane & Women's Hospital, Herston, QLD, Australia. Scott.Farrell@uq.edu.au., Sterling M; RECOVER Injury Research Centre, The University of Queensland, Level 7 STARS Hospital, 296 Herston Rd, Herston, QLD, 4029, Australia.; NHMRC Centre of Research Excellence: Better Health Outcomes for Compensable Injury, The University of Queensland, Herston, QLD, Australia., Klyne DM; NHMRC Centre of Clinical Research Excellence in Spinal Pain, Injury & Health; School of Health & Rehabilitation Sciences, The University of Queensland, St Lucia, QLD, Australia., Mustafa S; Davies Livestock Research Centre, The University of Adelaide, Roseworthy, SA, Australia., Campos AI; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, Australia.; Genetic Epidemiology Laboratory, Mental Health & Neuroscience Program, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia., Kho PF; Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.; Molecular Cancer Epidemiology Laboratory, Population Health Program, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.; School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia., Lundberg M; Institute of Biological Psychiatry, Boserupvej 2, 4000, Roskilde, Denmark.; Transformational Bioinformatics, CSIRO Health & Biosecurity, North Ryde, NSW, Australia.; UQ Diamantina Institute, The University of Queensland & Translational Research Institute, Woolloongabba, QLD, Australia., Rentería ME; Genetic Epidemiology Laboratory, Mental Health & Neuroscience Program, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia., Ngo TT; RECOVER Injury Research Centre, The University of Queensland, Level 7 STARS Hospital, 296 Herston Rd, Herston, QLD, 4029, Australia., Cuéllar-Partida G; UQ Diamantina Institute, The University of Queensland & Translational Research Institute, Woolloongabba, QLD, Australia.; Gilead Sciences, Foster City, CA, USA.
Jazyk: angličtina
Zdroj: 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 [Eur Spine J] 2023 Jun; Vol. 32 (6), pp. 2078-2085. Date of Electronic Publication: 2023 Apr 17.
DOI: 10.1007/s00586-023-07711-7
Abstrakt: 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 < 5%). Latent causal variable (LCV) and generalised summary data-based Mendelian randomisation (GSMR) analyses examined putative causal associations between chronic pain & CRP (FDR < 5%).
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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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