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Title: Variants in KCNJ11 and BAD do not predict response to ketogenic dietary therapies for epilepsy
Austin Authors: Schoeler, Natasha E;Leu, Costin;White, Jon;Plagnol, Vincent;Ellard, Sian;Matarin, Mar;Yellen, Gary;Thiele, Elizabeth A;Mackay, Mark;McMahon, Jacinta M;Scheffer, Ingrid E ;Sander, Josemir W;Cross, J Helen;Sisodiya, Sanjay M
Affiliation: NIHR University College London Hospitals Biomedical Research Centre, Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, UK
UCL Institute of Child Health, London, UK
Department of Genetics Environment and Evolution, UCL Genetics Institute, London, UK
Department of Statistical Genetics, University College London, London, UK
Molecular Genetics, University of Exeter Medical School, Exeter, UK
Department of Neurobiology, Harvard Medical School, Boston, MA, USA
Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
Royal Children's Hospital, Parkville, Victoria, Australia
Murdoch Children's Research Institute, Melbourne, Victoria, Australia
Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia
Departments of Medicine and Paediatrics, The University of Melbourne, Melbourne, Australia
Florey Institute of Neurosciences and Mental Health, Austin Health, Heidelberg, Victoria, Australia
The Epilepsy Society, Chalfont-St-Peter, Bucks, UK
Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, The Netherlands
Great Ormond Street Hospital for Children, London, UK
Young Epilepsy, Lingfield, UK
Issue Date: Dec-2015 2015-10-24
Publication information: Epilepsy Research 2015; 118: 22-28
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.
DOI: 10.1016/j.eplepsyres.2015.10.003
ORCID: 0000-0002-2311-2174
PubMed URL:
Type: Journal Article
Subjects: BAD
Genetic biomarker
Ketogenic diet
Appears in Collections:Journal articles

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