Post-Traumatic Headache in Children and Genetic Risk of Migraine: An Observational Cohort Study

Abstract

Background and Objectives – To examine the association between genetic risk of migraine and post-traumatic headache (PTH) in children.Methods – This is a secondary analysis of a cohort study that recruited children aged 8–17 years within 48 hours of concussion or orthopedic injury (OI) from 5 pediatric emergency departments and followed them for 6 months. Genetic risk of migraine was estimated through (1) family history of migraine, (2) polygenic risk scores (PRSs), and (3) forty individual single-nucleotide polymorphisms (SNPs). PTH was categorized as: no PTH (no PTH), PTH nonmigraine phenotype (PTH-NM), or PTH migraine phenotype. Ordinal regression models with cluster-adjusted standard errors and restricted cubic splines were used to estimate associations between genetic risk of migraine and increasing severity of PTH (no PTH vs PTH-NM vs PTH migraine phenotype), adjusting for injury type (concussion vs OI), age, sex, time since injury, first principal component, deprivation indices, concussion history, and preinjury headache history.Results – The sample included 646 children (median [interquartile range] age = 12.38 [10.52–14.41] years, including 436 (67.5%) with concussion. Family history of migraine was associated with increasing severity of PTH in 2/5 models (rs7684253 model: χ2 = 3.99, df = 1, p = 0.046; rs75002882 model: χ2 = 4.02, df = 1, p = 0.045), while migraine PRS was not (χ2 = 12.95, df = 12, p = 0.373). Four SNPs were associated with increasing severity of PTH (rs13078967: χ2 = 103.87, df = 6, p < 0.001; rs7684253: χ2 = 12.90, df = 6, p = 0.045; rs2160875: χ2 = 17.35, df = 6, p = 0.008; and rs75002882: χ2 = 291.79, df = 6, p < 0.001) and 2 remained significant after Bonferroni correction (rs13078967 and rs75002882).Discussion – Four migraine susceptibility genetic variants were associated with PTH, as was family history of migraine in some models, but a migraine PRS was not.