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Variants in KCNJ11 and BAD do not predict response to ketogenic dietary therapies for epilepsy

Schoeler, NE; Leu, C; White, J; Plagnol, V; Ellard, S; Matarin, M; Yellen, G; ... Sisodiya, SM; + view all (2015) Variants in KCNJ11 and BAD do not predict response to ketogenic dietary therapies for epilepsy. Epilepsy Research , 118 pp. 22-28. 10.1016/j.eplepsyres.2015.10.003. Green open access

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Abstract

In the absence of specific metabolic disorders, predictors of response to ketogenic dietary therapies (KDT) are unknown. We aimed to determine whether variants in established candidate genes KCNJ11 and BAD influence response to KDT. We sequenced KCNJ11 and BAD in individuals without previously-known glucose transporter type 1 deficiency syndrome or other metabolic disorders, who received KDT for epilepsy. Hospital records were used to obtain demographic and clinical data. Two response phenotypes were used: ≥ 50% seizure reduction and seizure-freedom at 3-month follow-up. Case/control association tests were conducted with KCNJ11 and BAD variants with minor allele frequency (MAF)>0.01, using PLINK. Response to KDT in individuals with variants with MAF<0.01 was evaluated. 303 Individuals had KCNJ11 and 246 individuals had BAD sequencing data and diet response data. Six SNPs in KCNJ11 and two in BAD had MAF>0.01. Eight variants in KCNJ11 and seven in BAD (of which three were previously-unreported) had MAF<0.01. No significant results were obtained from association analyses, with either KDT response phenotype. P-values were similar when accounting for ethnicity using a stratified Cochran-Mantel-Haenszel test. There did not seem to be a consistent effect of rare variants on response to KDT, although the cohort size was too small to assess significance. Common variants in KCNJ11 and BAD do not predict response to KDT for epilepsy. We can exclude, with 80% power, association from variants with a MAF of >0.05 and effect size >3. A larger sample size is needed to detect associations from rare variants or those with smaller effect sizes.

Type: Article
Title: Variants in KCNJ11 and BAD do not predict response to ketogenic dietary therapies for epilepsy
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.eplepsyres.2015.10.003
Publisher version: http://dx.doi.org/10.1016/j.eplepsyres.2015.10.003
Language: English
Additional information: Copyright © 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). This document was posted here by permission of the publisher. At the time of the deposit, it included all changes made during peer review, copy editing, and publishing. The U. S. National Library of Medicine is responsible for all links within the document and for incorporating any publisher-supplied amendments or retractions issued subsequently. The published journal article, guaranteed to be such by Elsevier, is available for free, on ScienceDirect, at: http://dx.doi.org/10.1016/j.eplepsyres.2015.10.003
Keywords: BAD, Epilepsy, Genetic biomarker, KCNJ11, Ketogenic diet, Seizures
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Neurosciences Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1478955
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