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Epilepsy and autism spectrum disorder (ASD) often occur together in the same individual. However, it remains unknown whether siblings of children with ASD have an increased risk of epilepsy and vice versa. This study determines the risk of ASD and epilepsy among younger siblings of children with ASD and epilepsy.

The study included all children born in Denmark between January 1, 1980 and 31 December 2006 who participated in follow-up until December 31, 2012 (1,663,302 children). We used Cox regression to calculate the adjusted hazard ratio (aHR) and the Kaplan-Meier method to calculate the cumulative incidence.

The overall aHR of epilepsy in younger siblings increased by 70% (aHR 1.70, 95% confidence interval [CI] 1.34–2.16%) if the older sibling had ASD compared with siblings where the older sibling did not have ASD. The cumulative incidence of epilepsy at 20 years of age was 2.54% (95% CI 1.97–3.26%) if the older sibling had ASD, whereas the cumulative incidence of epilepsy at 20 years of age was 1.63% (95% CI 1.60–1.66%) if the older sibling did not have ASD. The overall aHR of ASD in younger siblings increased by 54% if the older sibling had epilepsy (aHR 1.54, 95% CI 1.32–1.80) compared with siblings where the older sibling did not have epilepsy. The cumulative incidence of ASD at 20 years of age was 2.06% (95% CI 1.84–2.32%) if the older sibling had epilepsy, whereas the cumulative incidence of ASD at 20 years of age was 1.27% (95% CI 1.25–1.29%) if the older sibling did not have epilepsy.

The cross-disorder sibling risk of epilepsy and ASD was increased for the two disorders, which suggests that genes or environmental factors shared by family members may play a causal role in the co-occurrence of ASD and epilepsy.