Linkage and association analysis of CACNG3 in childhood absence epilepsy

Kate V. Everett; Barry Chioza; Jean Aicardi; Harald Aschauer; Oebele Brouwer; Petra Callenbach; Athanasios Covanis; Olivier Dulac; Orvar Eeg-Olofsson; Martha Feucht; Mogens Friis; Francoise Goutieres; Renzo Guerrini; Armin Heils; Marianne Kjeldsen; Anna-Elina Lehesjoki; Andrew Makoff; Rima Nabbout; Ingrid Olsson; Thomas Sander; Auli Siren; Paul McKeigue; Robert Robinson; Nichole Taske; Michele Rees; Mark Gardiner

doi:10.1038/sj.ejhg.5201783

Linkage and association analysis of CACNG3 in childhood absence epilepsy

Kate V. Everett^*, Barry Chioza, Jean Aicardi, Harald Aschauer, Oebele Brouwer, Petra Callenbach, Athanasios Covanis, Olivier Dulac, Orvar Eeg-Olofsson, Martha Feucht, Mogens Friis, Francoise Goutieres, Renzo Guerrini, Armin Heils, Marianne Kjeldsen, Anna-Elina Lehesjoki, Andrew Makoff, Rima Nabbout, Ingrid Olsson, Thomas SanderAuli Siren, Paul McKeigue, Robert Robinson, Nichole Taske, Michele Rees, Mark Gardiner

^*Corresponding author for this work

Faculty of Medical Sciences/UMCG

Research output: Contribution to journal › Article › Academic › peer-review

42 Citations (Scopus)

Abstract

Childhood absence epilepsy (CAE) is an idiopathic generalised epilepsy characterised by absence seizures manifested by transitory loss of awareness with 2.5 - 4 Hz spike - wave complexes on ictal EEG. A genetic component to aetiology is established but the mechanism of inheritance and the genes involved are not fully defined. Available evidence suggests that genes encoding brain expressed voltage-gated calcium channels, including CACNG3 on chromosome 16p12 - p13.1, may represent susceptibility loci for CAE. The aim of this work was to further evaluate CACNG3 as a susceptibility locus by linkage and association analysis. Assuming locus heterogeneity, a significant HLOD score (HLOD 3.54, a 0.62) was obtained for markers encompassing CACNG3 in 65 nuclear families with a proband with CAE. The maximum nonparametric linkage score was 2.87 (P > 0.002). Re-sequencing of the coding exons in 59 patients did not identify any putative causal variants. A linkage disequilibrium (LD) map of CACNG3 was constructed using 23 single nucleotide polymorphisms (SNPs). Transmission disequilibrium was sought using individual SNPs and SNP- based haplotypes with the pedigree disequilibrium test in 217 CAE trios and the 65 nuclear pedigrees. Evidence for transmission disequilibrium (P

Original language	English
Pages (from-to)	463-472
Number of pages	10
Journal	European Journal of Human Genetics
Volume	15
Issue number	4
DOIs	https://doi.org/10.1038/sj.ejhg.5201783
Publication status	Published - Apr-2007

Keywords

absence epilepsy
linkage
association
CACNG3
splice variants
IDIOPATHIC GENERALIZED EPILEPSY
PEDIGREE DISEQUILIBRIUM TEST
GENETIC-VARIATION
SEIZURES
CHANNEL
CACNA1H
MOUSE
MUTATIONS
RECEPTORS
VARIANTS

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Everett, K. V., Chioza, B., Aicardi, J., Aschauer, H., Brouwer, O., Callenbach, P., Covanis, A., Dulac, O., Eeg-Olofsson, O., Feucht, M., Friis, M., Goutieres, F., Guerrini, R., Heils, A., Kjeldsen, M., Lehesjoki, A.-E., Makoff, A., Nabbout, R., Olsson, I., ... Gardiner, M. (2007). Linkage and association analysis of CACNG3 in childhood absence epilepsy. European Journal of Human Genetics, 15(4), 463-472. https://doi.org/10.1038/sj.ejhg.5201783

@article{a13b0d3d4ff6464f9c7a5f79eeb92162,

title = "Linkage and association analysis of CACNG3 in childhood absence epilepsy",

abstract = "Childhood absence epilepsy (CAE) is an idiopathic generalised epilepsy characterised by absence seizures manifested by transitory loss of awareness with 2.5 - 4 Hz spike - wave complexes on ictal EEG. A genetic component to aetiology is established but the mechanism of inheritance and the genes involved are not fully defined. Available evidence suggests that genes encoding brain expressed voltage-gated calcium channels, including CACNG3 on chromosome 16p12 - p13.1, may represent susceptibility loci for CAE. The aim of this work was to further evaluate CACNG3 as a susceptibility locus by linkage and association analysis. Assuming locus heterogeneity, a significant HLOD score (HLOD 3.54, a 0.62) was obtained for markers encompassing CACNG3 in 65 nuclear families with a proband with CAE. The maximum nonparametric linkage score was 2.87 (P > 0.002). Re-sequencing of the coding exons in 59 patients did not identify any putative causal variants. A linkage disequilibrium (LD) map of CACNG3 was constructed using 23 single nucleotide polymorphisms (SNPs). Transmission disequilibrium was sought using individual SNPs and SNP- based haplotypes with the pedigree disequilibrium test in 217 CAE trios and the 65 nuclear pedigrees. Evidence for transmission disequilibrium (P",

keywords = "absence epilepsy, linkage, association, CACNG3, splice variants, IDIOPATHIC GENERALIZED EPILEPSY, PEDIGREE DISEQUILIBRIUM TEST, GENETIC-VARIATION, SEIZURES, CHANNEL, CACNA1H, MOUSE, MUTATIONS, RECEPTORS, VARIANTS",

author = "Everett, {Kate V.} and Barry Chioza and Jean Aicardi and Harald Aschauer and Oebele Brouwer and Petra Callenbach and Athanasios Covanis and Olivier Dulac and Orvar Eeg-Olofsson and Martha Feucht and Mogens Friis and Francoise Goutieres and Renzo Guerrini and Armin Heils and Marianne Kjeldsen and Anna-Elina Lehesjoki and Andrew Makoff and Rima Nabbout and Ingrid Olsson and Thomas Sander and Auli Siren and Paul McKeigue and Robert Robinson and Nichole Taske and Michele Rees and Mark Gardiner",

year = "2007",

month = apr,

doi = "10.1038/sj.ejhg.5201783",

language = "English",

volume = "15",

pages = "463--472",

journal = "European Journal of Human Genetics",

issn = "1018-4813",

publisher = "Nature Publishing Group",

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Everett, KV, Chioza, B, Aicardi, J, Aschauer, H, Brouwer, O , Callenbach, P, Covanis, A, Dulac, O, Eeg-Olofsson, O, Feucht, M, Friis, M, Goutieres, F, Guerrini, R, Heils, A, Kjeldsen, M, Lehesjoki, A-E, Makoff, A, Nabbout, R, Olsson, I, Sander, T, Siren, A, McKeigue, P, Robinson, R, Taske, N, Rees, M & Gardiner, M 2007, 'Linkage and association analysis of CACNG3 in childhood absence epilepsy', European Journal of Human Genetics, vol. 15, no. 4, pp. 463-472. https://doi.org/10.1038/sj.ejhg.5201783

TY - JOUR

T1 - Linkage and association analysis of CACNG3 in childhood absence epilepsy

AU - Everett, Kate V.

AU - Chioza, Barry

AU - Aicardi, Jean

AU - Aschauer, Harald

AU - Brouwer, Oebele

AU - Callenbach, Petra

AU - Covanis, Athanasios

AU - Dulac, Olivier

AU - Eeg-Olofsson, Orvar

AU - Feucht, Martha

AU - Friis, Mogens

AU - Goutieres, Francoise

AU - Guerrini, Renzo

AU - Heils, Armin

AU - Kjeldsen, Marianne

AU - Lehesjoki, Anna-Elina

AU - Makoff, Andrew

AU - Nabbout, Rima

AU - Olsson, Ingrid

AU - Sander, Thomas

AU - Siren, Auli

AU - McKeigue, Paul

AU - Robinson, Robert

AU - Taske, Nichole

AU - Rees, Michele

AU - Gardiner, Mark

PY - 2007/4

Y1 - 2007/4

N2 - Childhood absence epilepsy (CAE) is an idiopathic generalised epilepsy characterised by absence seizures manifested by transitory loss of awareness with 2.5 - 4 Hz spike - wave complexes on ictal EEG. A genetic component to aetiology is established but the mechanism of inheritance and the genes involved are not fully defined. Available evidence suggests that genes encoding brain expressed voltage-gated calcium channels, including CACNG3 on chromosome 16p12 - p13.1, may represent susceptibility loci for CAE. The aim of this work was to further evaluate CACNG3 as a susceptibility locus by linkage and association analysis. Assuming locus heterogeneity, a significant HLOD score (HLOD 3.54, a 0.62) was obtained for markers encompassing CACNG3 in 65 nuclear families with a proband with CAE. The maximum nonparametric linkage score was 2.87 (P > 0.002). Re-sequencing of the coding exons in 59 patients did not identify any putative causal variants. A linkage disequilibrium (LD) map of CACNG3 was constructed using 23 single nucleotide polymorphisms (SNPs). Transmission disequilibrium was sought using individual SNPs and SNP- based haplotypes with the pedigree disequilibrium test in 217 CAE trios and the 65 nuclear pedigrees. Evidence for transmission disequilibrium (P

AB - Childhood absence epilepsy (CAE) is an idiopathic generalised epilepsy characterised by absence seizures manifested by transitory loss of awareness with 2.5 - 4 Hz spike - wave complexes on ictal EEG. A genetic component to aetiology is established but the mechanism of inheritance and the genes involved are not fully defined. Available evidence suggests that genes encoding brain expressed voltage-gated calcium channels, including CACNG3 on chromosome 16p12 - p13.1, may represent susceptibility loci for CAE. The aim of this work was to further evaluate CACNG3 as a susceptibility locus by linkage and association analysis. Assuming locus heterogeneity, a significant HLOD score (HLOD 3.54, a 0.62) was obtained for markers encompassing CACNG3 in 65 nuclear families with a proband with CAE. The maximum nonparametric linkage score was 2.87 (P > 0.002). Re-sequencing of the coding exons in 59 patients did not identify any putative causal variants. A linkage disequilibrium (LD) map of CACNG3 was constructed using 23 single nucleotide polymorphisms (SNPs). Transmission disequilibrium was sought using individual SNPs and SNP- based haplotypes with the pedigree disequilibrium test in 217 CAE trios and the 65 nuclear pedigrees. Evidence for transmission disequilibrium (P

KW - absence epilepsy

KW - linkage

KW - association

KW - CACNG3

KW - splice variants

KW - IDIOPATHIC GENERALIZED EPILEPSY

KW - PEDIGREE DISEQUILIBRIUM TEST

KW - GENETIC-VARIATION

KW - SEIZURES

KW - CHANNEL

KW - CACNA1H

KW - MOUSE

KW - MUTATIONS

KW - RECEPTORS

KW - VARIANTS

U2 - 10.1038/sj.ejhg.5201783

DO - 10.1038/sj.ejhg.5201783

M3 - Article

SN - 1018-4813

VL - 15

SP - 463

EP - 472

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

IS - 4

ER -

Linkage and association analysis of CACNG3 in childhood absence epilepsy

Abstract

Keywords

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