Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins.

中文翻译：

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肌萎缩侧索硬化与癫痫的共同遗传风险分析

由于过度兴奋已被证明是一种共同的病理生理机制，我们使用最新和最大的全基因组研究来确定这些疾病之间的遗传重叠。首先，我们没有显示出显着的遗传相关性，当按次要等位基因频率分类时也是如此。其次，我们使用基因组风险评分分析确认不存在多基因重叠。最后，我们没有在这两种疾病的荟萃分析中发现多效性变异。我们的研究结果表明，肌萎缩侧索硬化和癫痫不具有共同的遗传风险，表明这两种疾病的过度兴奋具有不同的起源。