Genetic and environmental factors in febrile seizures: a Danish population-based twin study

The relative importance of genetic and environmental factors in the etiology of febrile seizures was estimated using a large, unselected population-based twin sample. A total of 34,076 twins (aged 12-41 years), recruited from the Danish Twin Registry, were screened for febrile seizures by questionnaire. Information was obtained from 11,872 complete pairs. Concordance rates, odds ratios and correlations were used to assess the degree of similarity in monozygotic (MZ) and dizygotic (DZ) twins. Model fitting and estimation of heritability (proportion of the population variance attributable to genetic variation) were performed using standard biometrical methods. Significantly higher probandwise concordance rates were found for MZ compared with DZ twins (0.36 and 0.12, P < 0.01). Odds ratios and correlations showed a similar pattern. An etiological model including additive genetic effects and individual-specific environmental factors provided the best fit to the data with a heritability for febrile seizures of 70% (95% CI: 61-77%). The remaining 30% of the variation could be attributed to individual-specific environmental factors. In conclusion, this study has confirmed a major impact of genetic factors in the etiology of febrile seizures. Future studies aimed at identifying the specific genetic factors and environmental exposures involved in determining febrile seizure risk are clearly warranted.