Department of Neurology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, China.
Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.
Sci Rep. 2022 Feb 15;12(1):2544. doi: 10.1038/s41598-022-06463-6.
Type 2 diabetes (T2D) and amyotrophic lateral sclerosis (ALS) are associated consistently. However, it is currently unknown whether this association is causal. We aimed to estimate the unconfounded, causal association between T2D on ALS using a two-sample Mendelian randomization approach both in European and East Asian ancestry. Genetic variants strongly associated with T2D and each T2D markers were used to investigate the effect of T2D on ALS risk in European (involving 20,806 ALS cases and 59,804 controls) and East Asian (involving 1234 ALS cases and 2850 controls) ancestry. We found that the OR of ALS per 1 SD increase in T2D was estimated to be 0.96 [95% confidence interval (CI) 0.92-0.996; p = 0.03] in European populations. Similarly, all 8 SNPs were associated with T2D in East Asian ancestry, the OR of ALS per 1 SD increase in T2D was estimated to be 0.83 [95% CI 0.70-0.992; p = 0.04] in East Asian populations. Examining the intercept estimates from MR-Egger regression also leads to the same conclusion, in that horizontal pleiotropy unlikely influences the results in either population. We found that genetically predicted T2D was associated with significantly lower odds of amyotrophic lateral sclerosis both in European and East Asian populations. It is now critical to identify a clear molecular explanation for this association between T2D and ALS and to focus on its potential therapeutic implications.
2 型糖尿病（T2D）和肌萎缩侧索硬化症（ALS）之间存在一致的关联。然而，目前尚不清楚这种关联是否具有因果关系。我们旨在使用两样本 Mendelian 随机化方法，在欧洲和东亚血统中，估计 T2D 对 ALS 的无混杂、因果关联。我们使用与 T2D 强烈相关的遗传变异和每个 T2D 标记物来研究 T2D 对欧洲（涉及 20806 例 ALS 病例和 59804 例对照）和东亚（涉及 1234 例 ALS 病例和 2850 例对照）血统中 ALS 风险的影响。我们发现，T2D 每增加 1 个标准差，ALS 的比值比估计为 0.96（95%置信区间 0.92-0.996；p=0.03）在欧洲人群中。同样，在东亚血统中，所有 8 个 SNP 都与 T2D 相关，T2D 每增加 1 个标准差，ALS 的比值比估计为 0.83（95%置信区间 0.70-0.992；p=0.04）在东亚人群中。从 MR-Egger 回归的截距估计中也可以得出同样的结论，即水平多效性不太可能影响这两个人群的结果。我们发现，遗传预测的 T2D 与欧洲和东亚人群中肌萎缩侧索硬化症的发病几率显著降低有关。现在的关键是要为 T2D 和 ALS 之间的这种关联找到一个明确的分子解释，并关注其潜在的治疗意义。
