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Genome-wide mega-analysis identifies 16 loci and highlights diverse biological mechanisms in the common epilepsies.

Publication ,  Journal Article
International League Against Epilepsy Consortium on Complex Epilepsies,
Published in: Nat Commun
December 10, 2018

The epilepsies affect around 65 million people worldwide and have a substantial missing heritability component. We report a genome-wide mega-analysis involving 15,212 individuals with epilepsy and 29,677 controls, which reveals 16 genome-wide significant loci, of which 11 are novel. Using various prioritization criteria, we pinpoint the 21 most likely epilepsy genes at these loci, with the majority in genetic generalized epilepsies. These genes have diverse biological functions, including coding for ion-channel subunits, transcription factors and a vitamin-B6 metabolism enzyme. Converging evidence shows that the common variants associated with epilepsy play a role in epigenetic regulation of gene expression in the brain. The results show an enrichment for monogenic epilepsy genes as well as known targets of antiepileptic drugs. Using SNP-based heritability analyses we disentangle both the unique and overlapping genetic basis to seven different epilepsy subtypes. Together, these findings provide leads for epilepsy therapies based on underlying pathophysiology.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

December 10, 2018

Volume

9

Issue

1

Start / End Page

5269

Location

England

Related Subject Headings

  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Linkage Disequilibrium
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Gene Frequency
  • Gene Expression Regulation
  • Epilepsy
 

Citation

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International League Against Epilepsy Consortium on Complex Epilepsies, . (2018). Genome-wide mega-analysis identifies 16 loci and highlights diverse biological mechanisms in the common epilepsies. Nat Commun, 9(1), 5269. https://doi.org/10.1038/s41467-018-07524-z
International League Against Epilepsy Consortium on Complex Epilepsies, Anthony L. “Genome-wide mega-analysis identifies 16 loci and highlights diverse biological mechanisms in the common epilepsies.Nat Commun 9, no. 1 (December 10, 2018): 5269. https://doi.org/10.1038/s41467-018-07524-z.
International League Against Epilepsy Consortium on Complex Epilepsies. Genome-wide mega-analysis identifies 16 loci and highlights diverse biological mechanisms in the common epilepsies. Nat Commun. 2018 Dec 10;9(1):5269.
International League Against Epilepsy Consortium on Complex Epilepsies, Anthony L. “Genome-wide mega-analysis identifies 16 loci and highlights diverse biological mechanisms in the common epilepsies.Nat Commun, vol. 9, no. 1, Dec. 2018, p. 5269. Pubmed, doi:10.1038/s41467-018-07524-z.
International League Against Epilepsy Consortium on Complex Epilepsies. Genome-wide mega-analysis identifies 16 loci and highlights diverse biological mechanisms in the common epilepsies. Nat Commun. 2018 Dec 10;9(1):5269.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

December 10, 2018

Volume

9

Issue

1

Start / End Page

5269

Location

England

Related Subject Headings

  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Linkage Disequilibrium
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Gene Frequency
  • Gene Expression Regulation
  • Epilepsy