Abstract
BackgroundLarge register-based studies have reported an association between head trauma and increased risk of multiple sclerosis (MS). We aimed to investigate possible interactions between head trauma and MS-associated HLA genes in relation to MS risk.MethodsWe used a Swedish population-based case-control study (2807 incident cases, 5950 matched controls with HLA genotypes available for 2057 cases, 2887 controls). Subjects with and without a history of self-reported head trauma were compared regarding MS risk, by calculating ORs with 95% CIs using logistic regression models. Additive interaction between head trauma,HLA-DRB1*1501and absence ofHLA-A*0201, was assessed by calculating the attributable proportion (AP) due to interaction.ResultsA history of head trauma was associated with a 30% increased risk of subsequently developing MS (OR 1.34, 95% CI 1.17 to 1.53), with a trend showing increased risk of MS with increasing number of head impacts (p=0.03). We observed synergistic effects between recent head trauma andHLA-DRB1*15:01as well as absence ofHLA*02:01in relation to MS risk (each AP 0.40, 95% CI 0.1 to 0.7). Recent head trauma in individuals with both genetic risk factors rendered an 18-fold increased risk of MS, compared with those with neither the genetic risk factors nor a history of head trauma (OR 17.7, 95% CI 7.13 to 44.1).ConclusionsOur findings align with previous observations of a dose-dependent association between head trauma and increased risk of MS and add a novel aspect of this association by revealing synergistic effects between recent head trauma and MS-associated HLA genes.
Funder
Swedish Brain Foundation
Swedish Research Council for Health, Working Life and Welfare
Swedish Foundation for MS Research
Swedish Research Council
NEURO Sweden
Ugglas Foundation, the Swedish Foundation for MS Research
Subject
Psychiatry and Mental health,Neurology (clinical),Surgery