Genetic variants associated with chronic postsurgical pain: evidence from the China Surgery and Anaesthesia Cohort study

Abstract

Background: Chronic postsurgical pain (CPSP) is one of the most common surgery-related complications and significantly impacts patient' quality of life. However, studies exploring the underlying genetics of postsurgical pain remain limited.

Methods: This study was based on 17 025 individuals from the China Surgery and Anaesthesia Cohort. We used the Brief Pain Inventory to measure pain intensity prospectively after surgery. CPSP was defined as a dichotomous (yes, no) or continuous (based on pain intensity) variable across surgeries (abdomen, thorax, head and neck, limbs and superficial body regions and other body areas) at 3 months, and persistent pain at various postsurgical follow-up assessments. Genome-wide association analyses were conducted in 9022 individuals with genotyping data.

Results: We identified 16 independent genome-wide significant loci associated with CPSP. Multiple approaches, including gene mapping, annotation, and multiomics colocalisation, prioritised several potential risk genes, such as ASTN1, RSU1, and C1QL3, involved in neuronal migration, extracellular signal-regulated kinase/mitogen-activated protein kinase signalling, and synaptic function. The single nucleotide polymorphism-based narrow-sense heritability was estimated to be 13.7% (5.1-22.4%) for CPSP defined as a continuous variable. The polygenic risk scores of post-traumatic stress disorder, pain all over the body, multisite chronic pain, and opioid dependence were associated with CPSP at a nominal significance level.

Conclusions: This study enhances our understanding of the genetic predisposition to chronic postsurgical pain.

Clinical trial registration: Chinese Clinical Trial Registry (ChiCTR2000034039).

Keywords: ASTN1; ERK signalling; NOS2; chronic postsurgical pain; genetics.