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. 2026 Jun:43:106260.
doi: 10.1016/j.jpain.2026.106260. Epub 2026 Mar 12.

Adolescent pain reports share genetic overlap with adult chronic pain conditions: A polygenic score analysis using the ABCD study

Lydia Rader  1 , Katerina Zorina-Lichtenwalter  2 , Daniel E Gustavson  3 , Tor D Wager  4 , Naomi P Friedman  3
Affiliations

Adolescent pain reports share genetic overlap with adult chronic pain conditions: A polygenic score analysis using the ABCD study

Lydia Rader et al. J Pain. 2026 Jun.

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.

Keywords: Adolescent; Chronic pain; Development; Genomic; Polygenic score.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1.
Figure 1.
A visualization of the bifactor-like genetic model of chronic pain. A bifactor-like genetic model of chronic pain was fit based on past literature (12). Each rectangle represents GWAS summary statistics of a pain condition. The General Chronic Pain circle represents a latent factor that is capturing the covariance of all 24 pain indicators. The Musculoskeletal Chronic Pain circle represents a latent factor that is capturing shared variance of 11 pain conditions. The numbers represent the strength of the loading onto the factor, with 0 being no shared covariance and 1.00 being full shared variance with the factor. The factors’ variances were standardized to 1. Residual correlations between some pain conditions were included. The residuals of each individual pain condition are not visualized, but can be found elsewhere (12). hdch = headache; mgrn = migraine; nksh = neck/shoulder; back = back; chDs = chest pain/discomfort; chPh = chest pain during physical activity; IBS = irritable bowel syndrome; gast = gastritis; oesp = oesophagitis; stmP = stomach pain; crpl = carpal tunnel; cyst = cystitis; hipP = hip pain; kneP = knee pain; legP = leg pain; gout = gout; enLL = enthesopathies of lower limb; hipA = hip arthrosis; kneA = knee arthrosis; enth = enthesopathies; otRA = rheumatoid arthritis; arth = arthropathies nonspecific including osteoarthritis; pnjt = pain in joint; CWP = chronic widespread pain.
Figure 2.
Figure 2.
The process of constructing polygenic scores. A Genome-Wide Association Study (GWAS) is conducted in a discovery sample to identify genetic risk variants associated with the trait of interest. The trait of interest can either be a case-control or continuous phenotype. The summary statistics from this GWAS are used to constructed weighted sums or alleles, or polygenic scores, in a target sample. The polygenic scores can then be associated to measured outcomes in the target sample to test for genetic associations.
Figure 3.
Figure 3.
Endorsed pain locations of adolescents at two timepoints split by sex The body maps visualize the locations of pain endorsement of adolescents who reported pain. Location(s) of pain was assessed using the pediatric adaptation of the Collaborative Health Outcomes Information Registry (Peds-CHOIR) body location map (21), which includes 74 locations that could be selected for females and males. At age 12, 1,804 females and 1,188 males report pain. At age 13, 1,118 females and 1,117 males report pain. The plots were generated using the R Package “CHOIRBM” (29–30).
See this image and copyright information in PMC

References

    1. Cohen SP, Vase L, Hooten WM. Chronic pain: An update on burden, best practices, and new advances. The Lancet. 2021;397(10289):2082–2097. doi: 10.1016/S0140-6736(21)00393-7 - DOI - PubMed
    1. King S, Chambers CT, Huguet A, et al. The epidemiology of chronic pain in children and adolescents revisited: A systematic review. PAIN. 2011;152(12):2729–2738. doi: 10.1016/j.pain.2011.07.016 - DOI - PubMed
    1. Murray CB, Groenewald CB, De La Vega R, Palermo TM. Long-term impact of adolescent chronic pain on young adult educational, vocational, and social outcomes. Pain. 2020;161(2):439–445. doi: 10.1097/j.pain.0000000000001732 - DOI - PMC - PubMed
    1. Groenewald CB, Law EF, Fisher E, Beals-Erickson SE, Palermo TM. Associations Between adolescent chronic pain and prescription opioid misuse in adulthood. The Journal of Pain. 2019;20(1):28–37. doi: 10.1016/j.jpain.2018.07.007 - DOI - PMC - PubMed
    1. Brattberg G Do pain problems in young school children persist into early adulthood? A 13-year follow-up. European Journal of Pain. 2004;8(3):187–199. doi: 10.1016/j.ejpain.2003.08.001 - DOI - PubMed

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