Application of rare variant transmission disequilibrium tests to epileptic encephalopathy trio sequence data

Epi4K Consortium, Epilepsy Phenome Genome Project, EuroEPINOMICS-RES Consortium, Joseph Sirven

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3 Scopus citations

Abstract

The classic epileptic encephalopathies, including infantile spasms (IS) and Lennox-Gastaut syndrome (LGS), are severe seizure disorders that usually arise sporadically. De novo variants in genes mainly encoding ion channel and synaptic proteins have been found to account for over 15% of patients with IS or LGS. The contribution of autosomal recessive genetic variation, however, is less well understood. We implemented a rare variant transmission disequilibrium test (TDT) to search for autosomal recessive epileptic encephalopathy genes in a cohort of 320 outbred patient-parent trios that were generally prescreened for rare metabolic disorders. In the current sample, our rare variant transmission disequilibrium test did not identify individual genes with significantly distorted transmission over expectation after correcting for the multiple tests. While the rare variant transmission disequilibrium test did not find evidence of a role for individual autosomal recessive genes, our current sample is insufficiently powered to assess the overall role of autosomal recessive genotypes in an outbred epileptic encephalopathy population.

Original languageEnglish (US)
Pages (from-to)894-899
Number of pages6
JournalEuropean Journal of Human Genetics
Volume25
Issue number7
DOIs
StatePublished - Jun 1 2017

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Epi4K Consortium, Epilepsy Phenome Genome Project, EuroEPINOMICS-RES Consortium, & Sirven, J. (2017). Application of rare variant transmission disequilibrium tests to epileptic encephalopathy trio sequence data. European Journal of Human Genetics, 25(7), 894-899. https://doi.org/10.1038/ejhg.2017.61