Pharmacoresponse in genetic generalized epilepsy: a genome-wide association study
Pharmacoresistance is a major burden in epilepsy treatment. We aimed to identify genetic biomarkers in response to specific antiepileptic drugs (AEDs) in genetic generalized epilepsies (GGE). We conducted a genome-wide association study (GWAS) of 3.3 million autosomal SNPs in 893 European subjects w...
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| Veröffentlicht in: | Pharmacogenomics 2020-04, Vol.21 (5), p.325-335 |
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| creator | Wolking, Stefan Schulz, Herbert Nies, Anne T McCormack, Mark Schaeffeler, Elke Auce, Pauls Avbersek, Andreja Becker, Felicitas Klein, Karl M Krenn, Martin Møller, Rikke S Nikanorova, Marina Weckhuysen, Sarah Consortium, EpiPGx Cavalleri, Gianpiero L Delanty, Norman Depondt, Chantal Johnson, Michael R Koeleman, Bobby Pc Kunz, Wolfram S Marson, Anthony G Sander, Josemir W Sills, Graeme J Striano, Pasquale Zara, Federico Zimprich, Fritz Weber, Yvonne G Krause, Roland Sisodiya, Sanjay Schwab, Matthias Sander, Thomas Lerche, Holger |
| description | Pharmacoresistance is a major burden in epilepsy treatment. We aimed to identify genetic biomarkers in response to specific antiepileptic drugs (AEDs) in genetic generalized epilepsies (GGE).
We conducted a genome-wide association study (GWAS) of 3.3 million autosomal SNPs in 893 European subjects with GGE – responsive or nonresponsive to lamotrigine, levetiracetam and valproic acid.
Our GWAS of AED response revealed suggestive evidence for association at 29 genomic loci (p |
| doi_str_mv | 10.2217/pgs-2019-0179 |
| format | Article |
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We conducted a genome-wide association study (GWAS) of 3.3 million autosomal SNPs in 893 European subjects with GGE – responsive or nonresponsive to lamotrigine, levetiracetam and valproic acid.
Our GWAS of AED response revealed suggestive evidence for association at 29 genomic loci (p <10
) but no significant association reflecting its limited power. The suggestive associations highlight candidate genes that are implicated in epileptogenesis and neurodevelopment.
This first GWAS of AED response in GGE provides a comprehensive reference of SNP associations for hypothesis-driven candidate gene analyses in upcoming pharmacogenetic studies.</description><identifier>ISSN: 1462-2416</identifier><identifier>EISSN: 1744-8042</identifier><identifier>DOI: 10.2217/pgs-2019-0179</identifier><identifier>PMID: 32308125</identifier><language>eng</language><publisher>England: Future Medicine Ltd</publisher><subject>antiepileptic drugs ; genetic generalized epilepsy ; GWAS ; lamotrigine ; levetiracetam ; pharmacoresistance ; valproic acid</subject><ispartof>Pharmacogenomics, 2020-04, Vol.21 (5), p.325-335</ispartof><rights>2020 Future Medicine Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c382t-d099012f19a600a32e54c4b849f2cd2dd5bb203e5535f042fabbd26269c69f2a3</citedby><cites>FETCH-LOGICAL-c382t-d099012f19a600a32e54c4b849f2cd2dd5bb203e5535f042fabbd26269c69f2a3</cites><orcidid>0000-0001-9938-7126 ; 0000-0002-1460-6623</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32308125$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wolking, Stefan</creatorcontrib><creatorcontrib>Schulz, Herbert</creatorcontrib><creatorcontrib>Nies, Anne T</creatorcontrib><creatorcontrib>McCormack, Mark</creatorcontrib><creatorcontrib>Schaeffeler, Elke</creatorcontrib><creatorcontrib>Auce, Pauls</creatorcontrib><creatorcontrib>Avbersek, Andreja</creatorcontrib><creatorcontrib>Becker, Felicitas</creatorcontrib><creatorcontrib>Klein, Karl M</creatorcontrib><creatorcontrib>Krenn, Martin</creatorcontrib><creatorcontrib>Møller, Rikke S</creatorcontrib><creatorcontrib>Nikanorova, Marina</creatorcontrib><creatorcontrib>Weckhuysen, Sarah</creatorcontrib><creatorcontrib>Consortium, EpiPGx</creatorcontrib><creatorcontrib>Cavalleri, Gianpiero L</creatorcontrib><creatorcontrib>Delanty, Norman</creatorcontrib><creatorcontrib>Depondt, Chantal</creatorcontrib><creatorcontrib>Johnson, Michael R</creatorcontrib><creatorcontrib>Koeleman, Bobby Pc</creatorcontrib><creatorcontrib>Kunz, Wolfram S</creatorcontrib><creatorcontrib>Marson, Anthony G</creatorcontrib><creatorcontrib>Sander, Josemir W</creatorcontrib><creatorcontrib>Sills, Graeme J</creatorcontrib><creatorcontrib>Striano, Pasquale</creatorcontrib><creatorcontrib>Zara, Federico</creatorcontrib><creatorcontrib>Zimprich, Fritz</creatorcontrib><creatorcontrib>Weber, Yvonne G</creatorcontrib><creatorcontrib>Krause, Roland</creatorcontrib><creatorcontrib>Sisodiya, Sanjay</creatorcontrib><creatorcontrib>Schwab, Matthias</creatorcontrib><creatorcontrib>Sander, Thomas</creatorcontrib><creatorcontrib>Lerche, Holger</creatorcontrib><title>Pharmacoresponse in genetic generalized epilepsy: a genome-wide association study</title><title>Pharmacogenomics</title><addtitle>Pharmacogenomics</addtitle><description>Pharmacoresistance is a major burden in epilepsy treatment. We aimed to identify genetic biomarkers in response to specific antiepileptic drugs (AEDs) in genetic generalized epilepsies (GGE).
We conducted a genome-wide association study (GWAS) of 3.3 million autosomal SNPs in 893 European subjects with GGE – responsive or nonresponsive to lamotrigine, levetiracetam and valproic acid.
Our GWAS of AED response revealed suggestive evidence for association at 29 genomic loci (p <10
) but no significant association reflecting its limited power. The suggestive associations highlight candidate genes that are implicated in epileptogenesis and neurodevelopment.
This first GWAS of AED response in GGE provides a comprehensive reference of SNP associations for hypothesis-driven candidate gene analyses in upcoming pharmacogenetic studies.</description><subject>antiepileptic drugs</subject><subject>genetic generalized epilepsy</subject><subject>GWAS</subject><subject>lamotrigine</subject><subject>levetiracetam</subject><subject>pharmacoresistance</subject><subject>valproic acid</subject><issn>1462-2416</issn><issn>1744-8042</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp1kMtLAzEQh4MotlaPXmWPXqLJJLttvEnxBQUV9ByyyWyN7MvNLlL_erO2evM0D775wXyEnHJ2AcDnl-06UGBcUcbnao9M-VxKumAS9mMvM6AgeTYhRyG8MwY8k-yQTAQItuCQTsnz05vpKmObDkPb1AETXydrrLH39qd2pvRf6BJsfYlt2FwlZtw3FdJP7zAxITTWm943dRL6wW2OyUFhyoAnuzojr7c3L8t7unq8e1her6gVC-ipY0oxDgVXJmPMCMBUWpkvpCrAOnAuzXNgAtNUpEV8pzB57iCDTNksIkbMyPk2t-2ajwFDrysfLJalqbEZggahQKZSSBZRukVt14TQYaHbzlem22jO9GhRR4t6tKhHi5E_20UPeYXuj_7VFgG1BYqhH6I567G2qLdTvPDW1_hP-DdPZYHS</recordid><startdate>20200401</startdate><enddate>20200401</enddate><creator>Wolking, Stefan</creator><creator>Schulz, Herbert</creator><creator>Nies, Anne T</creator><creator>McCormack, Mark</creator><creator>Schaeffeler, Elke</creator><creator>Auce, Pauls</creator><creator>Avbersek, Andreja</creator><creator>Becker, Felicitas</creator><creator>Klein, Karl M</creator><creator>Krenn, Martin</creator><creator>Møller, Rikke S</creator><creator>Nikanorova, Marina</creator><creator>Weckhuysen, Sarah</creator><creator>Consortium, EpiPGx</creator><creator>Cavalleri, Gianpiero L</creator><creator>Delanty, Norman</creator><creator>Depondt, Chantal</creator><creator>Johnson, Michael R</creator><creator>Koeleman, Bobby Pc</creator><creator>Kunz, Wolfram S</creator><creator>Marson, Anthony G</creator><creator>Sander, Josemir W</creator><creator>Sills, Graeme J</creator><creator>Striano, Pasquale</creator><creator>Zara, Federico</creator><creator>Zimprich, Fritz</creator><creator>Weber, Yvonne G</creator><creator>Krause, Roland</creator><creator>Sisodiya, Sanjay</creator><creator>Schwab, Matthias</creator><creator>Sander, Thomas</creator><creator>Lerche, Holger</creator><general>Future Medicine Ltd</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9938-7126</orcidid><orcidid>https://orcid.org/0000-0002-1460-6623</orcidid></search><sort><creationdate>20200401</creationdate><title>Pharmacoresponse in genetic generalized epilepsy: a genome-wide association study</title><author>Wolking, Stefan ; 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We aimed to identify genetic biomarkers in response to specific antiepileptic drugs (AEDs) in genetic generalized epilepsies (GGE).
We conducted a genome-wide association study (GWAS) of 3.3 million autosomal SNPs in 893 European subjects with GGE – responsive or nonresponsive to lamotrigine, levetiracetam and valproic acid.
Our GWAS of AED response revealed suggestive evidence for association at 29 genomic loci (p <10
) but no significant association reflecting its limited power. The suggestive associations highlight candidate genes that are implicated in epileptogenesis and neurodevelopment.
This first GWAS of AED response in GGE provides a comprehensive reference of SNP associations for hypothesis-driven candidate gene analyses in upcoming pharmacogenetic studies.</abstract><cop>England</cop><pub>Future Medicine Ltd</pub><pmid>32308125</pmid><doi>10.2217/pgs-2019-0179</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-9938-7126</orcidid><orcidid>https://orcid.org/0000-0002-1460-6623</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Pharmacogenomics, 2020-04, Vol.21 (5), p.325-335 |
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| language | eng |
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| source | PubMed Central |
| subjects | antiepileptic drugs genetic generalized epilepsy GWAS lamotrigine levetiracetam pharmacoresistance valproic acid |
| title | Pharmacoresponse in genetic generalized epilepsy: a genome-wide association study |
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