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



Allen, Andrew S, Berkovic, Samuel F, Bridgers, Joshua, Cossette, Patrick, Dlugos, Dennis, Epstein, Michael P, Glauser, Tracy, Goldstein, David B, Heinzen, Erin L, Jiang, Yu
et al (show 104 more authors) (2017) Application of rare variant transmission disequilibrium tests to epileptic encephalopathy trio sequence data. EUROPEAN JOURNAL OF HUMAN GENETICS, 25 (7). pp. 894-899.

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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.

Item Type: Article
Uncontrolled Keywords: Epi4K Consortium, EuroEPINOMICS-RES Consortium, Epilepsy Phenome Genome Project, Humans, Spasms, Infantile, Genetic Predisposition to Disease, Gene Frequency, Linkage Disequilibrium, Polymorphism, Genetic, Infant, Genome-Wide Association Study, Lennox Gastaut Syndrome
Depositing User: Symplectic Admin
Date Deposited: 03 Jan 2018 13:28
Last Modified: 19 Jan 2023 06:46
DOI: 10.1038/ejhg.2017.61
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3015343