Liu Renfu, Tian Yu, Zhang Xiangtao, Zhang Xiaodan, Lin Yuanxiang
Department of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian, China; Department of Neurosurgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, Fujian, China.
Department of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian, China; Department of Neurosurgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, Fujian, China; Fujian Provincial Institutes of Brain Disorders and Brain Sciences, First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian, China.
Epilepsy Behav. 2024 Dec;161:110111. doi: 10.1016/j.yebeh.2024.110111. Epub 2024 Nov 1.
Observational studies have consistently indicated a significant correlation between abnormal cardiac conditions and epilepsy. However, the association and direction of this relationship remain a subject of debate. This study employs a two-sample bidirectional Mendelian randomization (MR) approach to investigate the association between abnormal cardiac conditions and epilepsy.
Instrumental variables, represented by single nucleotide polymorphisms (SNPs) associated with epilepsy and various abnormal cardiac conditions, were derived from large-scale genome-wide association studies databases, including FinnGen and UK Biobank. Bidirectional MR analysis was conducted to estimate the association between epilepsy and abnormal cardiac conditions. Sensitivity analyses were performed using MR-Egger, weighted median, Inverse Variance Weighted, and MR pleiotropy residual sum and outlier methods.
The forward MR analysis suggested a potential positive effect of atrial fibrillation and flutter (AF) and valvular heart diseases (VHD) on the risk of epilepsy. Conversely, the reverse MR analysis indicated that epilepsy might increase the susceptibility to AF, VHD, and heart failure.
The findings support a bidirectional relationship between AF, VHD, and epilepsy, indicating that AF and VHD can elevate the risk of developing epilepsy, while epilepsy, in turn, can also increase the risk of developing AF and VHD. Furthermore, the study suggest that epilepsy may contribute to the development of heart failure. These results underscore the importance of screening for cardiac abnormalities in patients with epilepsy and vice versa, to better understand their clinical significance and potential as modifiable risk factors.
观察性研究一直表明心脏异常状况与癫痫之间存在显著相关性。然而，这种关系的关联及方向仍是一个有争议的话题。本研究采用两样本双向孟德尔随机化（MR）方法来探究心脏异常状况与癫痫之间的关联。
从包括芬兰基因库（FinnGen）和英国生物银行（UK Biobank）在内的大规模全基因组关联研究数据库中获取与癫痫和各种心脏异常状况相关的单核苷酸多态性（SNP）作为工具变量。进行双向MR分析以估计癫痫与心脏异常状况之间的关联。使用MR-Egger、加权中位数、逆方差加权以及MR多效性残差总和与离群值方法进行敏感性分析。
正向MR分析表明心房颤动和扑动（AF）以及心脏瓣膜病（VHD）对癫痫风险可能有正向影响。相反，反向MR分析表明癫痫可能增加患AF、VHD和心力衰竭的易感性。
研究结果支持AF、VHD与癫痫之间存在双向关系，表明AF和VHD可提高患癫痫的风险，而癫痫反过来也可增加患AF和VHD的风险。此外，该研究表明癫痫可能促使心力衰竭的发生。这些结果强调了对癫痫患者进行心脏异常筛查的重要性，反之亦然，以便更好地理解其临床意义以及作为可改变风险因素的潜力。
