基于孟德尔随机化的证据:线粒体和癫痫之间的因果关系OA

Objective:To explore the causal relationship between mitochondria and epilepsy using Mendelian randomization(MR).Methods:Single nucleotide polymorphisms(SNPs)significantly associated with mitochondrial abundance across 66 traits were utilized as instrumental variables.The inverse variance weighted(IVW)method,MR Egger regression,and weighted median approach were employed to determine the causal relationship between exposure factors and the onset of epilepsy.Additionally,Cochran's Q test,leave-one-out analysis,and MR-PRESSO were used to assess the robustness of the results.Results:Significant causal relationships were identified between three datasets and generalized epilepsy.The IVW results indicated that[pyruvate dehydrogenase(lipoamide)kinase isozyme 1]was associated with an increased risk of generalized epilepsy(OR=1.275,95％CI=1.056～1.540,PIVW=0.011,PFDR=0.017),rRNA methyltransferase 3 was also linked to a heightened risk of generalized epilepsy(OR=1.158,95％CI=1.002～1.338,PIVW=0.047,PFDR=0.047),while the essential MCU regulator was associated with a reduced risk of generalized epilepsy(OR=0.727,95％CI=0.578～0.915,PIVW=0.007,PFDR=0.020).Five datasets exhibited significant causal relationships with focal epilepsy.The IVW results revealed that ribosome recycling factor was associated with an increased risk of focal epilepsy(OR=1.085,95％CI=1.000～1.178,PIVW=0.049,PFDR=0.061),protein lysine deacylase Sirtuin 5 was also linked to a heightened risk of focal epilepsy(OR=1.080,95％CI=1.001～1.167,PIVM=0.048,PFDR=0.079),complement component 1 Q subcomponent-binding protein was associated with a reduced risk of focal epilepsy(OR=0.917,95％CI=0.861～0.977,PIVW=0.007,PDDR=0.018),serine--tRNA ligase was also linked to a decreased risk of focal epilepsy(OR=0.852,95％CI=0.779～0.934,PIVW=0.001,PFDR=0.003),and NFU1 iron-sulfur cluster scaffold homolog was associated with an increased risk of focal epilepsy(OR=1.098,95％CI=1.000～1.204,PIVW=0.049,PFDR=0.049).Sensitivity tests confirmed the robustness of the findings(all P＞0.05).Conclusion:A causal relationship between mitochondria and epilepsy has been established.