目的:采用孟德尔随机化(Mendelian randomization,MR)研究方法分析炎症性肠病(inflammatory bowel disease,lBD)与癲痫之间的因果关系。

方法:将来自国际 IBD 遗传学联盟全基因组关联研究(Genome-Wide Association Studies,GWAS)的炎症性肠病包括病例组 25042 例和对照组 34915例中密切相关的遗传单核苷酸多态性( single nucleotide polymorphism,SNP)位点作为工具变量,与来自国际抗癫痫联盟包括病例组 15212 例和对照组 29677 例癫痫的遗传数据进行双样本的 MR 分析。主要随机效应模型的逆方差加权(inverse variance weighted,IVW )进行分析,并以 MR-Egger 回归法作为补充，OR 值作为结果呈现。

结果:共获得了 70 个与癫痫密切相关的 SNP 这一工具变量,IN 结果( OR=0.98,95% CI为 0.96~0.99,P=0.01)表明,基因预测 IBD 与癲痫的发病风险显著相关。MR-Egger 回归结果(P=0.77)和 PRESSO 检验表明研究结果不存在基因水平多效性,MR 分析结果稳健。

结论:遗传学预测的 IBD 与癲痫有因果关联,rs212402 变异可能是 IBD 影响癫痫发病的关键所在。

Objective: To investigate the causal role with Inflammatory bowel disease(lBD) and epilepsy through Mendelian randomization (MR) approach.

Methods: Genetic association data for IBD were collected through the International IBD Genetics Consortium (25 042 cases and 34 915 controls) and genetic association data for epilepsy were from International League Against Epilepsy Consortium (15212 cases and 29677 controls) MR analyses were performed using the summary level data for  epilepsy extracted above genetic association data to obtain the causal estimates. The inverse variance weighting (IVW) method  of the random effects model was the main analysis method supplemented by the WME and MR-Egger methods, the OR value was used to present the results.

Results: A total of 70 single nucleotide polymorphism(SNP) closely associated with epilepsy as instrumental variables from the pooled database were obtained,and the IVW results OR=0.98,95% C: 0.96~0.99,P=0.01) indicated that genes predicted IBD has a causal relationship with epilepsy. MR-Egger regression results(P=0.77) and PRESS0 test indicated that there was no horizontal pleiotropy of genes in our findings.

Conclusion: There is a causal association between epilepsy and lBD, and the variant of rs212402 may be the key to lBD affecting epilepsy.