Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Neurobiol Aging. 2020 Aug;92:153.e1-153.e5. doi: 10.1016/j.neurobiolaging.2020.04.011. Epub 2020 Apr 18.
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.
因为超兴奋性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肌萎缩侧索硬化症（n=36052）和癫痫（n=38349）全基因组研究来确定这些病症之间的遗传重叠。首先，我们表明即使按次要等位基因频率划分，也没有显著的遗传相关性。其次，我们使用基因组风险评分分析证实了不存在多基因重叠。最后，我们在这两种疾病的荟萃分析中没有发现多效变异。我们的研究结果表明肌萎缩侧索硬化症和癫痫症没有共同的遗传风险，表明两种疾病的超兴奋性具有不同的起源。
