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Genome-wide association analysis of idiopathic epilepsy in the Belgian shepherd

机译:比利时牧羊犬特发性癫痫的基因组关联分析

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Abstract Background Idiopathic epilepsy (IE) is a common neurological disorder in the domestic dog, and is defined as repeated seizure activity having no identifiable underlying cause. Some breeds, such as the Belgian shepherd dog, have a greater prevalence of the disorder. Previous studies in this and other breeds have identified ADAM23 as a gene that confers risk of IE, although additional loci are known to exist. The present study sought to identify additional loci that influence IE in the Belgian shepherd dog. Results Genome-wide association studies (GWAS) revealed a significant association between IE and CFA 14 ( p ?1.03 E ??08 ) and a suggestive association on CFA 37 ( p ?2.91 E ??06 ) in a region in linkage disequilibrium with ADAM23 . Logistic regression identified a 2-loci model that demonstrated interaction between the two chromosomal regions that when combined predicted IE risk with high sensitivity. Conclusions Two interacting loci, one each on CFAs 14 and 37, predictive of IE in the Belgian shepherd were identified. The loci are adjacent to potential candidate genes associated with neurological function. Further exploration of the region is warranted to identify causal variants underlying the association. Additionally, although the two loci were very good at predicting IE, they failed to capture all the risk, indicating additional loci or incomplete penetrance are also likely contributing to IE expression in the Belgian shepherd dog.
机译:摘要背景特发性癫痫(即)是国内狗的常见神经障碍,并且被定义为重复的癫痫发作活动,没有可识别的潜在原因。一些品种,如比利时牧羊犬,对这种疾病的流行率更大。以前的研究和其他品种已经鉴定了ADAM23作为赋予IE风险的基因,尽管已知存在额外的基因座。本研究试图确定影响比利时牧羊犬的其他基因座。结果基因组关联研究(GWAS)揭示了IE和CFA 14之间的显着关联(P <β1.03e-08),以及CFA 37的暗示结合(p <β.x≤2.91e'06)中的联系区域用Adam23不平衡。 Logistic回归鉴定了2-LOCI模型,其在组合预测的两个染色体区域之间的相互作用,即具有高灵敏度的风险。结论鉴定了两个在CFA14和37上的一个相互作用的基因座,鉴定了在比利时牧羊犬中的预测性。基因座与与神经功能相关的潜在候选基因相邻。有必要进一步探索该地区,以识别协会基础的因果变量。此外,虽然两个基因座非常擅长预测IE,但是他们未能捕获所有风险,表明其他基因座或不完全穿透也可能导致比利时牧羊犬的表达。

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