Abstracts

Rationale: Previous studies of familial risk in the epilepsies have been limited by small samples size, restriction to specific epilepsy subtypes, or biased sampling schemes. Also, many studies have used family history reports from probands to identify affected relatives, which is likely to result in recall bias and underreporting. Population-based studies of adequate size with a representative sample of phenotypes are needed to eliminate selection bias and provide accurate estimates of risk that can be used for genetic counseling. Methods: This study used data from the Genetic Epidemiology of Seizure Disorders in Rochester study (GESDR), a population-based investigation using the resources of the Rochester Epidemiology Project. The GESDR epilepsy probands comprise all 660 Rochester residents born ?1920 with incidence of epilepsy (?2 unprovoked seizures) from 1935-1994. Occurrence of epilepsy in the first-degree relatives of these probands was ascertained by reviewing the relatives medical records. Relatives were considered to be at risk of developing epilepsy from age at first residency in the local area until age at last residency, death, study end, or epilepsy diagnosis, whichever was earliest. Survival analysis methods were used to estimate cumulative incidence of epilepsy to age 40 in siblings and offspring of probands with epilepsy, within strata defined by the proband s epilepsy syndrome, sex, and age at epilepsy onset. We also calculated standardized incidence ratios (SIRs), using the population incidence rates from Rochester, MN as the reference. Results: The risk of epilepsy to age 40 in the general population of Rochester, MN was 1.4%. Risks were increased in relatives of probands with epilepsy (siblings 4.6%, offspring 3.9%), and the magnitude of increased risk varied according to proband epilepsy type, proband sex, and relative type. The greatest increases in risk were for relatives of probands with idiopathic generalized epilepsies (siblings 8.2%, offspring 8.2%). Among relatives of probands with focal epilepsy of unknown cause, risks were significantly increased in offspring (risk=3.5%, SIR=3.5) but not in siblings (risk=1.0%, SIR=1.1). Among the relatives of probands with focal epilepsy of structural/metabolic cause, risks were comparable to population rates (siblings 1.9%, offspring 2.4%). Risks in siblings were significantly increased in the families of both female (5.8%) and male probands (3.5%). However, risks in offspring were increased only in the families of female probands (5.3%) and not in the families of male probands (1.9%). Conclusions: The GESDR study addresses the shortcomings of previous studies by using a population-based design and rigorous data collection methodology. These data provide accurate estimates of familial risk that can inform epilepsy research and genetic counseling.