Adolescent pain reports share genetic overlap with adult chronic pain conditions: A polygenic score analysis using the ABCD study.
Journal Article
Overview
abstract
Adolescent pain complaints may be related to genetic risk for chronic pain across the life course. Identifying whether adolescent pain is genetically linked to chronic pain in adulthood can advance understanding of pain etiology and inform early intervention. Two waves of pain assessments were used from the Adolescent Brain Cognitive Development (ABCD) study, a population-based sample of 11,876 adolescents. The analyses included 6,387 adolescents of European-like ancestry (mean ages = 12.03 and 12.93 at waves 2 and 3; 52% males), with 94.0% retention across waves. Two polygenic scores (PGSs) were constructed using genome-wide association study summary statistics from up to 435,917 adults in the UK Biobank. One PGS captured shared genetic risk across 24 pain conditions (General Chronic Pain), while the second captured additional musculoskeletal-specific genetic risk across 11 conditions after adjusting for general pain (Musculoskeletal-specific Pain). Mixed-effects models were used to examine associations between these PGSs and adolescent self-reported pain presence, intensity, recurrence, and multi-site pain. Across both waves, 36.0%-37.0% adolescents reported pain. The General Pain PGS was associated with pain presence (b=0.07, OR=1.07, 95%CI=1.02-1.13, FDR-corrected p=0.023) and intensity (b=0.14, 95%CI=0.07-0.21, FDR-corrected p<0.001); but not recurrent pain (b=0.08, OR=1.08, 95%CI=1.01-1.16, FDR-corrected p=0.091) or multi-site pain (b=0.01, OR=1.00, 95%CI=0.94-1.07, FDR-corrected p=0.958). The Musculoskeletal-specific Pain PGS was not significantly associated with the outcomes. Genetic risk for chronic pain in adulthood, as measured by PGSs, is associated with adolescent pain complaints. Adolescent pain signals early vulnerability for chronic pain, highlighting adolescence for early intervention. PERSPECTIVE: This study links adolescent pain to polygenic risk for adult chronic pain, suggesting that early pain reflects enduring genetic liability and reflects central pain processes. These results provide mechanistic insight into chronic pain across the lifespan and highlight adolescence as a period for intervention.
