Pharmacoresponse in genetic generalized epilepsy: a genome-wide association study.
Pharmacoresponse in genetic generalized epilepsy: a genome-wide association study.
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DOI：
10.2217/pgs-2019-0179
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发表时间：
2020-04
期刊：
影响因子：
2.1
通讯作者：
S. Wolking;H. Schulz;A. Nies;M. McCormack;E. Schaeffeler;P. Auce;A. Avbersek;F. Becker;K. Klein;M. Krenn;R. Møller;M. Nikanorova;S. Weckhuysen;Epi4K Consortium;G. Cavalleri;N. Delanty;C. Depondt;Michael R. Johnson;B. Koeleman;W. Kunz;A. Marson;Josemir W Sander;G. Sills;P. Striano;F. Zara;F. Zimprich;Y. Weber;R. Krause;S. Sisodiya;M. Schwab;T. Sander;H. Lerche
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文献类型：
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作者：
S. Wolking;H. Schulz;A. Nies;M. McCormack;E. Schaeffeler;P. Auce;A. Avbersek;F. Becker;K. Klein;M. Krenn;R. Møller;M. Nikanorova;S. Weckhuysen;Epi4K Consortium;G. Cavalleri;N. Delanty;C. Depondt;Michael R. Johnson;B. Koeleman;W. Kunz;A. Marson;Josemir W Sander;G. Sills;P. Striano;F. Zara;F. Zimprich;Y. Weber;R. Krause;S. Sisodiya;M. Schwab;T. Sander;H. Lerche
目的：药物耐药性是癫痫治疗的主要负担。我们的目的是确定遗传性全身性癫痫（GGE）对特异性抗癫痫药物（AED）反应的遗传生物标志物。材料和方法：我们在893名对拉莫三嗪、左乙拉西坦和丙戊酸敏感或不敏感的GGE欧洲受试者中进行了330万个常染色体SNP的全基因组关联研究（GWAS）。结果如下：我们的AED反应的GWAS揭示了在29个基因组位点的相关性的提示性证据（p <10-5），但没有显著的相关性，反映了其有限的能力。提示性关联突出了与癫痫发生和神经发育有关的候选基因。结论：GGE中AED反应的第一个GWAS为即将到来的药物遗传学研究中假设驱动的候选基因分析提供了SNP关联的全面参考。
Aim: 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). Materials & methods: 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. Results: Our GWAS of AED response revealed suggestive evidence for association at 29 genomic loci (p <10-5) but no significant association reflecting its limited power. The suggestive associations highlight candidate genes that are implicated in epileptogenesis and neurodevelopment. Conclusion: 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.