Familial aggregation and severity of epilepsy

Genetic models for complex diseases frequently assume that genetic factors play a greater role in severe forms than in mild forms of disease. This study examined familial aggregation of epilepsy in relation to two measures of severity: duration and remission. The study population comprised 358 offspring born in Rochester, MN, U.S.A., to parents with epilepsy who were diagnosed in Rochester between 1935 and 1979 and followed for greater than or equal to 5 years after the first seizure. Cox proportional hazards analysis was used to examine the effects of duration of the parent's epilepsy (less than 5 vs. greater than or equal to 5 years) and remission of the parent's epilepsy (greater than or equal to 5 years seizure-free) on risk of unprovoked seizures in offspring. The univariate rate ratio (RR) for parent's duration (long vs. short) was 1.1 (95% confidence interval 0.32-3.57). The RR for parent's remission was 2.5 (0.55-11.41), reflecting a higher risk for offspring of remitting parents, which was not statistically significant. Multivariate analysis was used to control for three other parental attributes associated with offspring seizure risk: sex, age at onset of seizures (less than 20 vs. greater than or equal to 20 years), and seizure type (absence vs. other). The RR for duration was not substantially changed in this analysis (1.2; 0.37-4.16). However, the RR for remission dropped to 1.2 (0.25-5.97), suggesting that the higher risk in offspring of remitting parents was largely explained by confounding with other factors that influence offspring seizure risk.(ABSTRACT TRUNCATED AT 250 WORDS)