Genome-wide association study: Exploring the genetic basis for responsiveness to ketogenic dietary therapies for drug-resistant epilepsy.

Epilepsia
Natasha E SchoelerSanjay M Sisodiya

Abstract

With the exception of specific metabolic disorders, predictors of response to ketogenic dietary therapies (KDTs) are unknown. We aimed to determine whether common variation across the genome influences the response to KDT for epilepsy. We genotyped individuals who were negative for glucose transporter type 1 deficiency syndrome or other metabolic disorders, who received KDT for epilepsy. Genotyping was performed with the Infinium HumanOmniExpressExome Beadchip. Hospital records were used to obtain demographic and clinical data. KDT response (≥50% seizure reduction) at 3-month follow-up was used to dissect out nonresponders and responders. We then performed a genome-wide association study (GWAS) in nonresponders vs responders, using a linear mixed model and correcting for population stratification. Variants with minor allele frequency <0.05 and those that did not pass quality control filtering were excluded. After quality control filtering, the GWAS of 112 nonresponders vs 123 responders revealed an association locus at 6p25.1, 61 kb upstream of CDYL (rs12204701, P = 3.83 × 10-8 , odds ratio [A] = 13.5, 95% confidence interval [CI] 4.07-44.8). Although analysis of regional linkage disequilibrium around rs12204701 did not strengt...Continue Reading

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Citations

Mar 12, 2020·Frontiers in Cell and Developmental Biology·Xiaowei ZhouAijun Zhang
Sep 3, 2020·Nutrients·Alberto VerrottiGiovanni Farello
Feb 2, 2021·BMJ Nutrition, Prevention & Health·Lucia AronicaDominic P D'agostino
Dec 17, 2020·Metabolites·Antonio NapolitanoRaffaella Cusmai

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Methods Mentioned

BETA
blood drawn
DNAseq

Software Mentioned

Intropolis
Michigan Imputation Server
Stata
Alamut
Minimac3
Eagle
LMM
PLINK
GenomeStudio
ShapeIT

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