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

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Title: Genome‐wide association study: Exploring the genetic basis for responsiveness to ketogenic dietary therapies for drug‐resistant epilepsy.
Authors: Schoeler, Natasha E., Leu, Costin, Balestrini, Simona, Mudge, Jonathan M., Steward, Charles A., Frankish, Adam, Leung, Mary‐Anne, Mackay, Mark, Scheffer, Ingrid, Williams, Ruth, Sander, Josemir W., Cross, J. Helen, Sisodiya, Sanjay M.
Source: Epilepsia (Series 4). Aug2018, Vol. 59 Issue 8, p1557-1566. 10p.
Subjects: Ketogenic diet, Diet in disease, Drug resistance, Epilepsy, Epilepsy research
Abstract: Summary: Objective: 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. Methods: 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. Results: 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 strengthen the likelihood of CDYL being the candidate gene, additional bioinformatic analyses suggest it is the most likely candidate. Significance: CDYL deficiency has been shown to disrupt neuronal migration and to influence susceptibility to epilepsy in mice. Further exploration with a larger replication cohort is warranted to clarify whether CDYL is the causal gene underlying the association signal. [ABSTRACT FROM AUTHOR]
Copyright of Epilepsia (Series 4) is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Genome‐wide association study: Exploring the genetic basis for responsiveness to ketogenic dietary therapies for drug‐resistant epilepsy.
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  Data: &lt;searchLink fieldCode=&quot;JN&quot; term=&quot;%22Epilepsia+%28Series+4%29%22&quot;&gt;Epilepsia (Series 4)&lt;/searchLink&gt;. Aug2018, Vol. 59 Issue 8, p1557-1566. 10p.
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  Data: Summary: Objective: 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. Methods: 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 &lt;0.05 and those that did not pass quality control filtering were excluded. Results: 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 &#215; 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 strengthen the likelihood of CDYL being the candidate gene, additional bioinformatic analyses suggest it is the most likely candidate. Significance: CDYL deficiency has been shown to disrupt neuronal migration and to influence susceptibility to epilepsy in mice. Further exploration with a larger replication cohort is warranted to clarify whether CDYL is the causal gene underlying the association signal. [ABSTRACT FROM AUTHOR]
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  Data: &lt;i&gt;Copyright of Epilepsia (Series 4) is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder&#39;s express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.&lt;/i&gt; (Copyright applies to all Abstracts.)
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        Value: 10.1111/epi.14516
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        Text: English
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      – SubjectFull: Ketogenic diet
        Type: general
      – SubjectFull: Diet in disease
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      – SubjectFull: Drug resistance
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      – SubjectFull: Epilepsy
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              Text: Aug2018
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