PDF(Pubmed)
Abstract：
Studies suggest that amyotrophic lateral sclerosis (ALS) compromises the integrity of white matter fiber tracts, primarily affecting motor fibers. However, it remains uncertain whether the integrity of these fibers influences the risk of ALS. We performed bidirectional two-sample Mendelian randomization (MR) and multivariable MR analyses to evaluate the associative relationships between the integrity of fiber tracts [including the corticospinal tract (CST) and corpus callosum (CC)] and the risk of ALS. Genetic instrumental variables for specific fiber tracts were obtained from published genome-wide association studies (GWASs), including 33,292 European individuals from five diffusion magnetic resonance imaging (dMRI) datasets. Summary-level GWAS data for ALS were derived from 27,205 ALS patients and 110,881 controls. The MR results suggested that an increase in the first principal component (PC1) of fractional anisotropy (FA) in the genu of the CC (GCC) was correlated with an increased risk of ALS (PFDR = 0.001, odds ratio = 1.363, 95% confidence interval 1.178-1.577). Although other neuroimaging phenotypes [mean diffusivity in the CST, radial diffusivity (RD) in the CST, FA in the GCC, PC1 in the body of the CC (BCC), PC1 in the CST, and RD in the GCC] did not pass correction, they were also considered to have suggestive associations with the risk of ALS. No evidence revealed that ALS caused changes in the integrity of fiber tracts. In summary, the results of this study provide genetic support for the potential association between the integrity of specific fiber tracts and the risk of ALS. Greater fiber integrity in the GCC and BCC may be a risk factor for ALS, while greater fiber integrity in the CST may have a protective effect on ALS. This study provides insights into ALS development.
摘要：
研究表明，肌萎缩侧索硬化症（ALS）损害了白质纤维束的完整性，主要影响电机纤维。然而,尚不确定这些纤维的完整性是否会影响ALS的风险。我们进行了双向双样本孟德尔随机化（MR）和多变量MR分析，以评估纤维束（包括皮质脊髓束（CST）和call体（CC））的完整性与ALS风险之间的关联关系。从已发表的全基因组关联研究（GWAS）获得了特定纤维束的遗传工具变量，包括来自五个扩散磁共振成像（dMRI）数据集的33,292名欧洲个体。ALS的汇总水平GWAS数据来自27,205名ALS患者和110,881名对照。MR结果表明，CC（GCC）类型中分数各向异性（FA）的第一主成分（PC1）的增加与ALS的风险增加相关（PFDR=0.001，比值比=1.363，95％置信区间1.178-1.577）。尽管其他神经影像学表型[CST中的平均扩散率，CST中的径向扩散率(RD)，海湾合作委员会中的FA，CC(BCC)正文中的PC1，CST中的PC1，和RD在GCC]没有通过修正，他们也被认为与ALS的风险有暗示性关联.没有证据表明ALS引起纤维束完整性的变化。总之,这项研究的结果为特定纤维束的完整性与ALS风险之间的潜在关联提供了遗传支持.GCC和BCC中更高的纤维完整性可能是ALS的风险因素，而CST中更大的纤维完整性可能对ALS具有保护作用。这项研究提供了对ALS发展的见解。
