• Eva Johansson, Lars Alfredsson, Pernilla Strid, Ingrid Kockum, Tomas Olsson, and Anna Karin Hedström.
• Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
• J. Neurol. Neurosurg. Psychiatr. 2024 May 14; 95 (6): 554560554-560.

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*1501 and absence of HLA-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 and HLA-DRB1*15:01 as well as absence of HLA*02:01 in 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.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.

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