Familial risk of epilepsy: A population-based study

Anna L. Peljto, Christie Barker-Cummings, Vincent M. Vasoli, Cynthia L. Leibson, W. Allen Hauser, Jeffrey R. Buchhalter, Ruth Ottman

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Almost all previous studies of familial risk of epilepsy have had potentially serious methodological limitations. Our goal was to address these limitations and provide more rigorous estimates of familial risk in a population-based study. We used the unique resources of the Rochester Epidemiology Project to identify all 660 Rochester, Minnesota residents born in 1920 or later with incidence of epilepsy from 1935-94 (probands) and their 2439 first-degree relatives who resided in Olmsted County. We assessed incidence of epilepsy in relatives by comprehensive review of the relatives' medical records, and estimated age-specific cumulative incidence and standardized incidence ratios for epilepsy in relatives compared with the general population, according to proband and relative characteristics. Among relatives of all probands, cumulative incidence of epilepsy to age 40 was 4.7%, and risk was increased 3.3-fold (95% confidence interval 2.75-5.99) compared with population incidence. Risk was increased to the greatest extent in relatives of probands with idiopathic generalized epilepsies (standardized incidence ratio 6.0) and epilepsies associated with intellectual or motor disability presumed present from birth, which we denoted 'prenatal/developmental cause' (standardized incidence ratio 4.3). Among relatives of probands with epilepsy without identified cause (including epilepsies classified as 'idiopathic' or 'unknown cause'), risk was significantly increased for epilepsy of prenatal/developmental cause (standardized incidence ratio 4.1). Similarly, among relatives of probands with prenatal/developmental cause, risk was significantly increased for epilepsies without identified cause (standardized incidence ratio 3.8). In relatives of probands with generalized epilepsy, standardized incidence ratios were 8.3 (95% confidence interval 2.93-15.31) for generalized epilepsy and 2.5 (95% confidence interval 0.92-4.00) for focal epilepsy. In relatives of probands with focal epilepsy, standardized incidence ratios were 1.0 (95% confidence interval 0.00-2.19) for generalized epilepsy and 2.6 (95% confidence interval 1.19-4.26) for focal epilepsy. Epilepsy incidence was greater in offspring of female probands than in offspring of male probands, and this maternal effect was restricted to offspring of probands with focal epilepsy. The results suggest that risks for epilepsies of unknown and prenatal/developmental cause may be influenced by shared genetic mechanisms. They also suggest that some of the genetic influences on generalized and focal epilepsies are distinct. However, the similar increase in risk for focal epilepsy among relatives of probands with either generalized (2.5-fold) or focal epilepsy (2.6-fold) may reflect some coexisting shared genetic influences.

Original languageEnglish (US)
Pages (from-to)795-805
Number of pages11
JournalBrain
Volume137
Issue number3
DOIs
StatePublished - Mar 2014

Fingerprint

Epilepsy
Partial Epilepsy
Incidence
Population
Generalized Epilepsy
Confidence Intervals
Familial
Medical Records
Epidemiology
Parturition
Causes

Keywords

  • epidemiology
  • epilepsy
  • familial aggregation
  • familial risk
  • genetics

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Peljto, A. L., Barker-Cummings, C., Vasoli, V. M., Leibson, C. L., Hauser, W. A., Buchhalter, J. R., & Ottman, R. (2014). Familial risk of epilepsy: A population-based study. Brain, 137(3), 795-805. https://doi.org/10.1093/brain/awt368

Familial risk of epilepsy : A population-based study. / Peljto, Anna L.; Barker-Cummings, Christie; Vasoli, Vincent M.; Leibson, Cynthia L.; Hauser, W. Allen; Buchhalter, Jeffrey R.; Ottman, Ruth.

In: Brain, Vol. 137, No. 3, 03.2014, p. 795-805.

Research output: Contribution to journalArticle

Peljto, AL, Barker-Cummings, C, Vasoli, VM, Leibson, CL, Hauser, WA, Buchhalter, JR & Ottman, R 2014, 'Familial risk of epilepsy: A population-based study', Brain, vol. 137, no. 3, pp. 795-805. https://doi.org/10.1093/brain/awt368
Peljto AL, Barker-Cummings C, Vasoli VM, Leibson CL, Hauser WA, Buchhalter JR et al. Familial risk of epilepsy: A population-based study. Brain. 2014 Mar;137(3):795-805. https://doi.org/10.1093/brain/awt368
Peljto, Anna L. ; Barker-Cummings, Christie ; Vasoli, Vincent M. ; Leibson, Cynthia L. ; Hauser, W. Allen ; Buchhalter, Jeffrey R. ; Ottman, Ruth. / Familial risk of epilepsy : A population-based study. In: Brain. 2014 ; Vol. 137, No. 3. pp. 795-805.
@article{2fcb9acaa2304184a1643d45bfc95553,
title = "Familial risk of epilepsy: A population-based study",
abstract = "Almost all previous studies of familial risk of epilepsy have had potentially serious methodological limitations. Our goal was to address these limitations and provide more rigorous estimates of familial risk in a population-based study. We used the unique resources of the Rochester Epidemiology Project to identify all 660 Rochester, Minnesota residents born in 1920 or later with incidence of epilepsy from 1935-94 (probands) and their 2439 first-degree relatives who resided in Olmsted County. We assessed incidence of epilepsy in relatives by comprehensive review of the relatives' medical records, and estimated age-specific cumulative incidence and standardized incidence ratios for epilepsy in relatives compared with the general population, according to proband and relative characteristics. Among relatives of all probands, cumulative incidence of epilepsy to age 40 was 4.7{\%}, and risk was increased 3.3-fold (95{\%} confidence interval 2.75-5.99) compared with population incidence. Risk was increased to the greatest extent in relatives of probands with idiopathic generalized epilepsies (standardized incidence ratio 6.0) and epilepsies associated with intellectual or motor disability presumed present from birth, which we denoted 'prenatal/developmental cause' (standardized incidence ratio 4.3). Among relatives of probands with epilepsy without identified cause (including epilepsies classified as 'idiopathic' or 'unknown cause'), risk was significantly increased for epilepsy of prenatal/developmental cause (standardized incidence ratio 4.1). Similarly, among relatives of probands with prenatal/developmental cause, risk was significantly increased for epilepsies without identified cause (standardized incidence ratio 3.8). In relatives of probands with generalized epilepsy, standardized incidence ratios were 8.3 (95{\%} confidence interval 2.93-15.31) for generalized epilepsy and 2.5 (95{\%} confidence interval 0.92-4.00) for focal epilepsy. In relatives of probands with focal epilepsy, standardized incidence ratios were 1.0 (95{\%} confidence interval 0.00-2.19) for generalized epilepsy and 2.6 (95{\%} confidence interval 1.19-4.26) for focal epilepsy. Epilepsy incidence was greater in offspring of female probands than in offspring of male probands, and this maternal effect was restricted to offspring of probands with focal epilepsy. The results suggest that risks for epilepsies of unknown and prenatal/developmental cause may be influenced by shared genetic mechanisms. They also suggest that some of the genetic influences on generalized and focal epilepsies are distinct. However, the similar increase in risk for focal epilepsy among relatives of probands with either generalized (2.5-fold) or focal epilepsy (2.6-fold) may reflect some coexisting shared genetic influences.",
keywords = "epidemiology, epilepsy, familial aggregation, familial risk, genetics",
author = "Peljto, {Anna L.} and Christie Barker-Cummings and Vasoli, {Vincent M.} and Leibson, {Cynthia L.} and Hauser, {W. Allen} and Buchhalter, {Jeffrey R.} and Ruth Ottman",
year = "2014",
month = "3",
doi = "10.1093/brain/awt368",
language = "English (US)",
volume = "137",
pages = "795--805",
journal = "Brain",
issn = "0006-8950",
publisher = "Oxford University Press",
number = "3",

}

TY - JOUR

T1 - Familial risk of epilepsy

T2 - A population-based study

AU - Peljto, Anna L.

AU - Barker-Cummings, Christie

AU - Vasoli, Vincent M.

AU - Leibson, Cynthia L.

AU - Hauser, W. Allen

AU - Buchhalter, Jeffrey R.

AU - Ottman, Ruth

PY - 2014/3

Y1 - 2014/3

N2 - Almost all previous studies of familial risk of epilepsy have had potentially serious methodological limitations. Our goal was to address these limitations and provide more rigorous estimates of familial risk in a population-based study. We used the unique resources of the Rochester Epidemiology Project to identify all 660 Rochester, Minnesota residents born in 1920 or later with incidence of epilepsy from 1935-94 (probands) and their 2439 first-degree relatives who resided in Olmsted County. We assessed incidence of epilepsy in relatives by comprehensive review of the relatives' medical records, and estimated age-specific cumulative incidence and standardized incidence ratios for epilepsy in relatives compared with the general population, according to proband and relative characteristics. Among relatives of all probands, cumulative incidence of epilepsy to age 40 was 4.7%, and risk was increased 3.3-fold (95% confidence interval 2.75-5.99) compared with population incidence. Risk was increased to the greatest extent in relatives of probands with idiopathic generalized epilepsies (standardized incidence ratio 6.0) and epilepsies associated with intellectual or motor disability presumed present from birth, which we denoted 'prenatal/developmental cause' (standardized incidence ratio 4.3). Among relatives of probands with epilepsy without identified cause (including epilepsies classified as 'idiopathic' or 'unknown cause'), risk was significantly increased for epilepsy of prenatal/developmental cause (standardized incidence ratio 4.1). Similarly, among relatives of probands with prenatal/developmental cause, risk was significantly increased for epilepsies without identified cause (standardized incidence ratio 3.8). In relatives of probands with generalized epilepsy, standardized incidence ratios were 8.3 (95% confidence interval 2.93-15.31) for generalized epilepsy and 2.5 (95% confidence interval 0.92-4.00) for focal epilepsy. In relatives of probands with focal epilepsy, standardized incidence ratios were 1.0 (95% confidence interval 0.00-2.19) for generalized epilepsy and 2.6 (95% confidence interval 1.19-4.26) for focal epilepsy. Epilepsy incidence was greater in offspring of female probands than in offspring of male probands, and this maternal effect was restricted to offspring of probands with focal epilepsy. The results suggest that risks for epilepsies of unknown and prenatal/developmental cause may be influenced by shared genetic mechanisms. They also suggest that some of the genetic influences on generalized and focal epilepsies are distinct. However, the similar increase in risk for focal epilepsy among relatives of probands with either generalized (2.5-fold) or focal epilepsy (2.6-fold) may reflect some coexisting shared genetic influences.

AB - Almost all previous studies of familial risk of epilepsy have had potentially serious methodological limitations. Our goal was to address these limitations and provide more rigorous estimates of familial risk in a population-based study. We used the unique resources of the Rochester Epidemiology Project to identify all 660 Rochester, Minnesota residents born in 1920 or later with incidence of epilepsy from 1935-94 (probands) and their 2439 first-degree relatives who resided in Olmsted County. We assessed incidence of epilepsy in relatives by comprehensive review of the relatives' medical records, and estimated age-specific cumulative incidence and standardized incidence ratios for epilepsy in relatives compared with the general population, according to proband and relative characteristics. Among relatives of all probands, cumulative incidence of epilepsy to age 40 was 4.7%, and risk was increased 3.3-fold (95% confidence interval 2.75-5.99) compared with population incidence. Risk was increased to the greatest extent in relatives of probands with idiopathic generalized epilepsies (standardized incidence ratio 6.0) and epilepsies associated with intellectual or motor disability presumed present from birth, which we denoted 'prenatal/developmental cause' (standardized incidence ratio 4.3). Among relatives of probands with epilepsy without identified cause (including epilepsies classified as 'idiopathic' or 'unknown cause'), risk was significantly increased for epilepsy of prenatal/developmental cause (standardized incidence ratio 4.1). Similarly, among relatives of probands with prenatal/developmental cause, risk was significantly increased for epilepsies without identified cause (standardized incidence ratio 3.8). In relatives of probands with generalized epilepsy, standardized incidence ratios were 8.3 (95% confidence interval 2.93-15.31) for generalized epilepsy and 2.5 (95% confidence interval 0.92-4.00) for focal epilepsy. In relatives of probands with focal epilepsy, standardized incidence ratios were 1.0 (95% confidence interval 0.00-2.19) for generalized epilepsy and 2.6 (95% confidence interval 1.19-4.26) for focal epilepsy. Epilepsy incidence was greater in offspring of female probands than in offspring of male probands, and this maternal effect was restricted to offspring of probands with focal epilepsy. The results suggest that risks for epilepsies of unknown and prenatal/developmental cause may be influenced by shared genetic mechanisms. They also suggest that some of the genetic influences on generalized and focal epilepsies are distinct. However, the similar increase in risk for focal epilepsy among relatives of probands with either generalized (2.5-fold) or focal epilepsy (2.6-fold) may reflect some coexisting shared genetic influences.

KW - epidemiology

KW - epilepsy

KW - familial aggregation

KW - familial risk

KW - genetics

UR - http://www.scopus.com/inward/record.url?scp=84894573349&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84894573349&partnerID=8YFLogxK

U2 - 10.1093/brain/awt368

DO - 10.1093/brain/awt368

M3 - Article

C2 - 24468822

AN - SCOPUS:84894573349

VL - 137

SP - 795

EP - 805

JO - Brain

JF - Brain

SN - 0006-8950

IS - 3

ER -