Genetic Variation in PADI6-PADI4 on 1p36.13 Is Associated with Common Forms of Human Generalized Epilepsy.
Genetic Variation in PADI6-PADI4 on 1p36.13 Is Associated with Common Forms of Human Generalized Epilepsy.
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DOI：
10.3390/genes12091441
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发表时间：
2021-09-18
期刊：
影响因子：
3.5
通讯作者：
Hakonarson H
中科院分区：
文献类型：
--
作者：
Buono RJ;Bradfield JP;Wei Z;Sperling MR;Dlugos DJ;Privitera MD;French JA;Lo W;Cossette P;Schachter SC;Basehore H;Lohoff FW;Grant SFA;Ferraro TN;Hakonarson H
我们进行了全基因组关联研究（GWAS），以确定与常见形式的特发性全身性癫痫（GE）和局灶性癫痫（FE）相关的遗传变异。使用2220名患者和14,448名对照者的队列，我们搜索了与GE、FE以及两种形式结合相关的单核苷酸多态性（SNP）。当比较所有病例与所有对照组时，我们没有发现任何达到全基因组统计学显著性（p ≤ 5 × 10−8）的SNP，并且比较FE病例与对照组时，很少有感兴趣的SNP。然而，我们记录了PADI 6-PADI 4基因中的多个连锁SNP，这些SNP达到了全基因组意义，并且在将单独的GE病例与对照进行比较时与疾病相关。PADI基因编码的酶在与组蛋白和自身抗体形成的表观遗传调控相关的分子途径中将精氨酸脱亚氨基化为瓜氨酸。虽然癫痫的遗传学和治疗主要集中在离子通道和神经递质机制上，但这些结果表明，基因表达的表观遗传控制和自身抗体的形成也可能在癫痫发生中发挥作用。
We performed a genome-wide association study (GWAS) to identify genetic variation associated with common forms of idiopathic generalized epilepsy (GE) and focal epilepsy (FE). Using a cohort of 2220 patients and 14,448 controls, we searched for single nucleotide polymorphisms (SNPs) associated with GE, FE and both forms combined. We did not find any SNPs that reached genome-wide statistical significance (p ≤ 5 × 10−8) when comparing all cases to all controls, and few SNPs of interest comparing FE cases to controls. However, we document multiple linked SNPs in the PADI6-PADI4 genes that reach genome-wide significance and are associated with disease when comparing GE cases alone to controls. PADI genes encode enzymes that deiminate arginine to citrulline in molecular pathways related to epigenetic regulation of histones and autoantibody formation. Although epilepsy genetics and treatment are focused strongly on ion channel and neurotransmitter mechanisms, these results suggest that epigenetic control of gene expression and the formation of autoantibodies may also play roles in epileptogenesis.
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影响因子：
12.8
作者：
Acharya, Nimish K.;Nagele, Eric P.;Nagele, Robert G.
通讯作者：
Nagele, Robert G.
影响因子：
56.9
作者：
Wang, Y;Wysocka, J;Coonrod, SA
通讯作者：
Coonrod, SA
DOI：
10.1093/bioinformatics/btq340
发表时间：
2010-09-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Willer CJ;Li Y;Abecasis GR
通讯作者：
Abecasis GR
影响因子：
2.2
作者：
Banerjee, Poonam Nina;Filippi, David;Hauser, W. Allen
通讯作者：
Hauser, W. Allen
影响因子：
2.2
作者：
Buono, RJ;Lohoff, FW;Ferraro, TN
通讯作者：
Ferraro, TN