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

2.50
Hdl Handle:
http://hdl.handle.net/11287/618133
Title:
Variants in KCNJ11 and BAD do not predict response to ketogenic dietary therapies for epilepsy.
Authors:
Schoeler, N. E.; Leu, C.; White, J.; Plagnol, V.; Ellard, Sian ( 0000-0002-7620-5526 ) ; Matarin, M.; Yellen, G.; Thiele, E. A.; Mackay, M.; McMahon, J. M.; Scheffer, I. E.; Sander, J. W.; Cross, J. H.; Sisodiya, S. M.
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.
Citation:
Variants in KCNJ11 and BAD do not predict response to ketogenic dietary therapies for epilepsy. 2015, 118:22-8 Epilepsy Res.
Publisher:
Elsevier
Journal:
Epilepsy research
Issue Date:
Dec-2015
URI:
http://hdl.handle.net/11287/618133
DOI:
10.1016/j.eplepsyres.2015.10.003
PubMed ID:
26590798
Additional Links:
http://linkinghub.elsevier.com/retrieve/pii/S0920-1211(15)30058-9
Note:
This article is freely available via Open Access, click on the 'Additional Link' above to access the full text.
Type:
Journal Article; Research Support, Non-U.S. Gov't
Language:
en
ISSN:
1872-6844
Appears in Collections:
2015 RD&E publications; Molecular Genetics

Full metadata record

DC FieldValue Language
dc.contributor.authorSchoeler, N. E.en
dc.contributor.authorLeu, C.en
dc.contributor.authorWhite, J.en
dc.contributor.authorPlagnol, V.en
dc.contributor.authorEllard, Sianen
dc.contributor.authorMatarin, M.en
dc.contributor.authorYellen, G.en
dc.contributor.authorThiele, E. A.en
dc.contributor.authorMackay, M.en
dc.contributor.authorMcMahon, J. M.en
dc.contributor.authorScheffer, I. E.en
dc.contributor.authorSander, J. W.en
dc.contributor.authorCross, J. H.en
dc.contributor.authorSisodiya, S. M.en
dc.date.accessioned2016-08-10T09:24:20Z-
dc.date.available2016-08-10T09:24:20Z-
dc.date.issued2015-12-
dc.identifier.citationVariants in KCNJ11 and BAD do not predict response to ketogenic dietary therapies for epilepsy. 2015, 118:22-8 Epilepsy Res.en
dc.identifier.issn1872-6844-
dc.identifier.pmid26590798-
dc.identifier.doi10.1016/j.eplepsyres.2015.10.003-
dc.identifier.urihttp://hdl.handle.net/11287/618133-
dc.description.abstractIn 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.en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urlhttp://linkinghub.elsevier.com/retrieve/pii/S0920-1211(15)30058-9en
dc.rightsArchived with thanks to Epilepsy researchen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.subjectWessex Classification Subject Headings::Neurologyen
dc.titleVariants in KCNJ11 and BAD do not predict response to ketogenic dietary therapies for epilepsy.en
dc.typeJournal Articleen
dc.typeResearch Support, Non-U.S. Gov'ten
dc.identifier.journalEpilepsy researchen
dc.description.noteThis article is freely available via Open Access, click on the 'Additional Link' above to access the full text.en
dc.type.versionPublisheden

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