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Published on: June 2, 2014
Post-Traumatic Headache in Children and Genetic Risk of Migraine: An Observational Cohort Study
Serena L Orr1,2,3,4, Andrew D Hershey5,6, Brad G Kurowski7
1Section of Neurology, Alberta Children's Hospital, Calgary, Alberta, Canada.
Insights
Genetic factors like family history and specific SNPs are linked to increased post-traumatic headache (PTH) severity in children. However, polygenic risk scores did not show a significant association in this study.
Area of Science:
- Genetics
- Pediatrics
- Neurology
Background:
- Post-traumatic headache (PTH) is a common consequence of head injuries in children.
- The role of genetic predisposition, particularly migraine susceptibility, in the development and severity of PTH is not fully understood.
- Investigating genetic risk factors may offer insights into PTH pathophysiology and identify at-risk individuals.
Purpose of the Study:
- To investigate the association between genetic risk factors for migraine and the severity of post-traumatic headache (PTH) in children.
- To determine if family history of migraine, polygenic risk scores (PRS), or specific single-nucleotide polymorphisms (SNPs) are associated with PTH phenotypes.
Main Methods:
- Secondary analysis of a cohort study involving 646 children (aged 8-17) within 48 hours of concussion or orthopedic injury.
- Genetic risk assessed via family history of migraine, migraine PRS, and 40 individual SNPs.
- PTH categorized into no PTH, nonmigraine PTH (PTH-NM), and migraine PTH phenotypes; ordinal regression models used for analysis.
Main Results:
- Family history of migraine showed an association with increasing PTH severity in some models (p=0.046, p=0.045).
- Migraine PRS was not significantly associated with PTH severity (p=0.373).
- Four specific SNPs (rs13078967, rs7684253, rs2160875, rs75002882) were associated with increased PTH severity, with two (rs13078967, rs75002882) remaining significant after Bonferroni correction.
Conclusions:
- Specific genetic variants associated with migraine susceptibility may play a role in the development of PTH in children.
- Family history of migraine may also be a contributing factor to PTH severity.
- Migraine polygenic risk scores did not appear to be a significant predictor of PTH severity in this pediatric cohort.
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.
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