Genome-wide association study suggests a critical contribution of the adaptive immune system to chronic post-surgical pain

Marc Parisien; Roel R I van Reij; Samar Khoury; Eda Koseli; Mohamad Karaky; Nynke J van den Hoogen; Garrie Peng; Massimo Allegri; Manuela de Gregori; Jacques E Chelly; Barbara A Rakel; Eske K Aasvang; Henrik Kehlet; Wolfgang F F A Buhre; Camron D Bryant; M Imad Damaj; Irah L King; Jeffrey S Mogil; Elbert A J Joosten; Luda Diatchenko

doi:10.1101/2023.01.24.23284520

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Genome-wide association study suggests a critical contribution of the adaptive immune system to chronic post-surgical pain

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Genome-wide association study suggests a critical contribution of the adaptive immune system to chronic post-surgical pain

Marc Parisien, Roel R I van Reij, Samar Khoury, Eda Koseli, Mohamad Karaky, Nynke J van den Hoogen, Garrie Peng, Massimo Allegri, Manuela de Gregori, Jacques E Chelly, …

medRxiv : the preprint server for health sciences

03/10/2023

DOI: 10.1101/2023.01.24.23284520

PMCID: PMC10029026

PMID: 36945481

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https://doi.org/10.1101/2023.01.24.23284520View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Chronic post-surgical pain affects a large proportion of people undergoing surgery, delaying recovery time and worsening quality of life. Although many environmental variables have been established as risk factors, less is known about genetic risk. To uncover genetic risk factors we performed genome-wide association studies in post-surgical cohorts of five surgery types- hysterectomy, mastectomy, abdominal, hernia, and knee- totaling 1350 individuals. Genetic associations between post-surgical chronic pain levels on a numeric rating scale (NRS) and additive genetic effects at common SNPs were evaluated. We observed genome-wide significant hits in almost all cohorts that displayed significance at the SNP, gene, and pathway levels. The cohorts were then combined via a GWAS meta-analysis framework for further analyses. Using partitioned heritability, we found that loci at genes specifically expressed in the immune system carried enriched heritability, especially genes related to B and T cells. The relevance of B cells in particular was then demonstrated in mouse postoperative pain assays. Taken altogether, our results suggest a role for the adaptive immune system in chronic post-surgical pain.

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Title: Subtitle: Genome-wide association study suggests a critical contribution of the adaptive immune system to chronic post-surgical pain
Creators: Marc Parisien - Edwards
Roel R I van Reij - Maastricht University
Samar Khoury - Edwards
Eda Koseli - Virginia Commonwealth University
Mohamad Karaky - Edwards
Nynke J van den Hoogen - Maastricht University
Garrie Peng
Massimo Allegri - Polyclinic Medical Center
Manuela de Gregori - Policlinico San Matteo Fondazione
Jacques E Chelly - University of Pittsburgh Medical Center
Barbara A Rakel - University of Iowa
Eske K Aasvang - Copenhagen University Hospital
Henrik Kehlet - Copenhagen University Hospital
Wolfgang F F A Buhre
Camron D Bryant - Boston University
M Imad Damaj
Irah L King
Jeffrey S Mogil - McGill University
Elbert A J Joosten - Maastricht University
Luda Diatchenko - Edwards
Resource Type: Preprint
Publication Details: medRxiv : the preprint server for health sciences
DOI: 10.1101/2023.01.24.23284520
PMID: 36945481
PMCID: PMC10029026
Language: English
Date posted: 03/10/2023
Academic Unit: Nursing; Physical Therapy and Rehabilitation Science
Record Identifier: 9984380658902771

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