ArticleFrontiers in genetics2021
Systems Biology Guided Gene Enrichment Approaches Improve Prediction of Chronic Post-surgical Pain After Spine Fusion.
Article in Frontiers in genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.
- Sex-specific pain management and outcomes in pediatric elective posterior spinal fusion: a database review.Spine deformity · 2026Pooled it
- Personalized Prediction of Acute and Chronic Postsurgical Pain - the role of Multidomain Biosignatures, Machine Learning-Based Integration, and Standardized Outcome Definitions.Current pain and headache reports · 2026Review
- Genome-wide association study on chronic postsurgical pain after abdominal surgeries in the UK Biobank.Anaesthesia · 2025Article
- Genome-wide association study on chronic postsurgical pain in the UK Biobank.British journal of anaesthesia · 2025Article
- Current Evidence for Biological Biomarkers and Mechanisms Underlying Acute to Chronic Pain Transition across the Pediatric Age Spectrum.Journal of clinical medicine · 2023Article
- Genetically modified mesenchymal stem cells promote spinal fusion through polarized macrophages.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- Genetic and epigenetic mechanisms influencing acute to chronic postsurgical pain transitions in pediatrics: Preclinical to clinical evidence.Canadian journal of pain = Revue canadienne de la douleur · 2022Review
- Predictors of Chronic Postsurgical Pain in Elderly Patients Undergoing Hip Arthroplasty: A Multi-Center Retrospective Cohort Study.International journal of general medicine · 2021Article
- Next-generation DNA methylation sequencing: loci and regions differentially methylated in adolescents with chronic postsurgical pain.Neurobiology of pain (Cambridge, Mass.)Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
objectivesIncorporation of genetic factors in psychosocial/perioperative models for predicting chronic postsurgical pain (CPSP) is key for personalization of analgesia. However, single variant associations with CPSP have small effect sizes, making polygenic risk assessment important. Unfortunately, pediatric CPSP studies are not sufficiently powered for unbiased genome wide association (GWAS). We previously leveraged systems biology to identify candidate genes associated with CPSP. The goal of this study was to use systems biology prioritized gene enrichment to generate polygenic risk scores (PRS) for improved prediction of CPSP in a prospectively enrolled clinical cohort.
methodsIn a prospectively recruited cohort of 171 adolescents (14.5 ± 1.8 years, 75.4% female) undergoing spine fusion, we collected data about anesthesia/surgical factors, childhood anxiety sensitivity (CASI), acute pain/opioid use, pain outcomes 6-12 months post-surgery and blood (for DNA extraction/genotyping). We previously prioritized candidate genes using computational approaches based on similarity for functional annotations with a literature-derived "training set." In this study, we tested ranked deciles of 1336 prioritized genes for increased representation of variants associated with CPSP, compared to 10,000 randomly selected control sets. Penalized regression (LASSO) was used to select final variants from enriched variant sets for calculation of PRS. PRS incorporated regression models were compared with previously published non-genetic models for predictive accuracy.
resultsIncidence of CPSP in the prospective cohort was 40.4%. 33,104 case and 252,590 control variants were included for association analyses. The smallest gene set enriched for CPSP had 80/1010 variants associated with CPSP ( DISCUSSION: Systems biology guided PRS improved predictive accuracy of CPSP risk in a pediatric cohort. They have potential to serve as biomarkers to guide risk stratification and tailored prevention. Findings highlight systems biology approaches for deriving PRS for phenotypes in cohorts less amenable to large scale GWAS.
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Registered trials
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