
浏览全部资源
扫码关注微信
1.510006 广州,广州中医药大学针灸康复临床医学院
2.400037 重庆,陆军军医大学(第三军医大学)第二附属医院儿科
3.400037 重庆,陆军军医大学(第三军医大学)第二附属医院神经外科全军癫痫诊治中心
[张春青,E-mail: cqzhang@tmmu.edu.cn ZHANG Chunqing, E-mail: cqzhang@tmmu.edu.cn
收稿:2024-03-03,
修回:2024-05-19,
纸质出版:2024-10-30
移动端阅览
舒昀, 袁青, 吴至凤, 等. 基于孟德尔随机化的缺血性脑卒中与癫痫的因果关系研究[J]. 陆军军医大学学报, 2024,46(20):2276-2283.
Yun SHU, Qing YUAN, Zhifeng WU, et al. Causality between ischemic stroke and epilepsy based on Mendelian randomization[J]. Journal of Army Medical University, 2024, 46(20): 2276-2283.
舒昀, 袁青, 吴至凤, 等. 基于孟德尔随机化的缺血性脑卒中与癫痫的因果关系研究[J]. 陆军军医大学学报, 2024,46(20):2276-2283. DOI: 10.16016/j.2097-0927.202403006.
Yun SHU, Qing YUAN, Zhifeng WU, et al. Causality between ischemic stroke and epilepsy based on Mendelian randomization[J]. Journal of Army Medical University, 2024, 46(20): 2276-2283. DOI: 10.16016/j.2097-0927.202403006.
目的
2
探索缺血性脑卒中与不同类型癫痫之间的因果关系,为缺血性脑卒中与癫痫的发病风险提供遗传学证据支持。
方法
2
基于全基因组关联分析的汇总数据,采用MR-Egger回归、加权中位数法、逆方差加权法进行孟德尔随机化(Mendelian randomization
MR)分析,使用MR-Egger回归检验、MR-PRESSO检验和留一法进行敏感性分析。
结果
2
两样本MR分析表明缺血性脑卒中与癫痫(
OR
=1.10,
P
=0.036)和全面性癫痫(
OR
=1.25,
P
=0.001)的风险表现出因果关系,但与局灶性癫痫(
OR
=1.06,
P
=0.360)之间未显现因果关系。另外,舒张压(
OR
=1.12,
P
=0.002)和BMI(
OR
=1.08,
P
=0.015)也与癫痫呈现因果关系,进一步使用多变量MR分析方法,校正混杂因素影响之后,只有缺血性脑卒中(
OR
=1.18,
P
=3.770×10
-6
)和癫痫风险之间呈现因果关系。
结论
2
缺血性脑卒中和全面性癫痫风险之间存在因果关联,可据此进行卒中后癫痫的风险分层。
Objective
2
To explore the causal relationship between ischemic stroke and different types of epilepsy so as to provide genetic evidence for the risk of epilepsy after ischemic stroke.
Methods
2
Based on the summary data of genome-wide association study
Mendelian randomization (MR) analysis was performed with MR-Egger regression
weighted median and inverse-variance weighting. Sensitivity analysis was conducted by using MR-Egger regression test
MR-PRESSO test and leave-one-out method.
Results
2
Two-sample MR analysis showed that there was a causal relationship between ischemic stroke and the risk of epilepsy (
OR
=1.10
P
=0.036) and generalized epilepsy (
OR
=1.25
P
=0.001)
but no such relationship was observed with the risk of focal epilepsy (
OR
=1.06
P
=0.360). In addition
diastolic blood pressure (
OR
=1.12
P
=0.002) and BMI (
OR
=1.08
P
=0.015) also had a causal relationship with the risk of epilepsy. After adjusting confounding factors
multivariate MR analysis revealed that only ischemic stroke (
OR
=1.18
P
=3.770×10
-6
) and epilepsy risk had a causal relationship.
Conclusion
2
There is a causal relationship between ischemic stroke and the risk of generalized epilepsy
which can be used to stratify the risk of post-stroke epilepsy.
KE B, LI C Y, SHANG H F. Sex hormones and risk of epilepsy: a bidirectional Mendelian randomization study[J]. Front Mol Neurosci, 2023, 16: 1153907. DOI: 10.3389/fnmol.2023.1153907.
VAN HEZIK-WESTER V, DE GROOT S, KANTERS T, et al . Burden of illness in people with medically refractory epilepsy who suffer from daily to weekly seizures: 12-month follow-up of participants in the EPISODE study[J ] . Front Neurol, 2022, 13: 1012486. DOI: 10.3389/fneur.2022.1012486.
WU S M, WU B, LIU M, et al . Stroke in China: advances and challenges in epidemiology, prevention, and management[J ] . Lancet Neurol, 2019, 18(4): 394-405. DOI: 10.1016/S1474-4 422(18)30500-3.
TRÖSCHER A R, GRUBER J, WAGNER J N, et al . Inflammation mediated epileptogenesis as possible mechanism underlying ischemic post-stroke epilepsy[J ] . Front Aging Neurosci, 2021, 13: 781174. DOI: 10.3389/fnagi.2021.781174.
MCDONALD T J W, HENRY-BARRON B J, FELTON E A, et al . Improving compliance in adults with epilepsy on a modified Atkins diet: a randomized trial[J ] . Seizure, 2018, 60: 132-138. DOI: 10.1016/j.seizure.2018.06.019.
RAZAZ N, TEDROFF K, VILLAMOR E, et al . Maternal body mass index in early pregnancy and risk of epilepsy in offspring[J ] . JAMA Neurol, 2017, 74(6): 668-676. DOI: 10.1001/jamaneurol.2016.6130.
STEFANIDOU M, HIMALI J J, DEVINSKY O, et al . Vascular risk factors as predictors of epilepsy in older age: the Framingham Heart Study[J ] . Epilepsia, 2022, 63(1): 237-243. DOI: 10.1111/epi.17108.
DOEGE C, LUEDDE M, KOSTEV K. Association between angiotensin receptor blocker therapy and incidence of epilepsy in patients with hypertension[J]. JAMA Neurol, 2022, 79(12): 1296-1302. DOI: 10.1001/jamaneurol.2022.3413.
RUSEK M, CZUCZWAR S J. A review of clinically significant drug-drug interactions involving angiotensin Ⅱ receptor antagonists and antiepileptic drugs[J]. Expert Opin Drug Metab Toxicol, 2020, 16(6): 507-515. DOI: 10.1080/17425255.2020.1763955.
ZHANG Z Z, WANG M M, YUAN S, et al . Alcohol, coffee,and milk intake in relation to epilepsy risk[J ] . Nutrients, 2022, 14(6): 1153. DOI: 10.3390/nu14061153.
ZENG Y J, CAO S, YANG H. Roles of gut microbiome in epilepsy risk: a Mendelian randomization study[J]. Front Microbiol, 2023, 14: 1115014. DOI: 10.3389/fmicb.2023.1115014.
MALIK R, CHAUHAN G, TRAYLOR M, et al . Multiancestry genome-wide association study of 520, 000 subjects identifies 32 loci associated with stroke and stroke subtypes[J ] . Nat Genet, 2018, 50(4): 524-537. DOI: 10.1038/s41588-018-0058-3.
YENGO L, SIDORENKO J, KEMPER K E, et al . Meta-analysis of genome-wide association studies for height and body mass index in~700000 individuals of European ancestry[J ] . Hum Mol Genet, 2018, 27(20): 3641-3649. DOI: 10.1093/hmg/ddy271.
International League Against Epilepsy Consortium on Complex Epilepsies. Genome-wide mega-analysis identifies 16 loci and highlights diverse biological mechanisms in the common epilepsies[J]. Nat Commun, 2018, 9(1): 5269. DOI: 10.1038/s41467-018-07524-z.
XIANG M M, WANG Y L, GAO Z Y, et al . Exploring causal correlations between inflammatory cytokines and systemic lupus erythematosus: a Mendelian randomization[J ] . Front Immunol, 2022, 13: 985729. DOI: 10.3389/fimmu.2022.985729.
PIERCE B L, AHSAN H, VANDERWEELE T J. Power and instrument strength requirements for Mendelian randomization studies using multiple genetic variants[J]. Int J Epidemiol, 2011, 40(3): 740-752. DOI: 10.1093/ije/dyq151.
BRION M J A, SHAKHBAZOV K, VISSCHER P M. Calculating statistical power in Mendelian randomization studies[J]. Int J Epidemiol, 2013, 42(5): 1497-1501. DOI: 10.1093/ije/dyt179.
BURGESS S, THOMPSON S G, CHD GENETICS COLLABORATION C R P. Avoiding bias from weak instruments in Mendelian randomization studies[J]. Int J Epidemiol, 2011, 40(3): 755-764. DOI: 10.1093/ije/dyr036.
PIERCE B L, BURGESS S. Efficient design for Mendelian randomization studies: subsample and 2-sample instrumental variable estimators[J]. Am J Epidemiol, 2013, 178(7): 1177-1184. DOI: 10.1093/aje/kwt084.
BURGESS S, THOMPSON S G. Interpreting findings from Mendelian randomization using the MR-Egger method[J]. Eur J Epidemiol, 2017, 32(5): 377-389. DOI: 10.1007/s10654-017-0255-x.
BOWDEN J, DAVEY SMITH G, BURGESS S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression[J]. Int J Epidemiol, 2015, 44(2): 512-525. DOI: 10.1093/ije/dyv080.
BOWDEN J, DAVEY SMITH G, HAYCOCK P C, et al . Consistent estimation in Mendelian randomization with some invalid instruments using a weighted Median estimator[J ] . Genet Epidemiol, 2016, 40(4): 304-314. DOI: 10.1002/gepi.21965.
BURGESS S, ZUBER V, GKATZIONIS A, et al . Modal-based estimationvia heterogeneity-penalized weighting: model averaging for consistent and efficient estimation in Mendelian randomization when a plurality of candidate instruments are valid[J ] . Int J Epidemiol, 2018, 47(4): 1242-1254. DOI: 10.1093/ije/dyy080.
VERBANCK M, CHEN C Y, NEALE B, et al . Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases[J ] . Nat Genet, 2018, 50(5): 693-698. DOI: 10.1038/s41588-018-0099-7.
BEGHI E, CARPIO A, FORSG REN L, et al . Recommendation for a definition of acute symptomatic seizure[J ] . Epilepsia, 2010, 51(4): 671-675. DOI: 10.1111/j.1528-1167.2009.02285.x.
GALOVIC M, FERREIRA-ATUESTA C, ABRAIRA L, et al . Seizures and epilepsy after stroke: epidemiology, biomarkers and management[J ] . Drugs Aging, 2021, 38(4): 285-299. DOI: 10.1007/s40266-021-00837-7.
DORIA J W, FORGACS P B. Incidence, implications, and management of seizures following ischemic and hemorrhagic stroke[J]. Curr Neurol Neurosci Rep, 2019, 19(7): 37. DOI: 10.1007/s11910-019-0957-4.
Dziadkowiak E, Guzinski M, Chojdak-Lukasiewicz J, et al . Predictive factors in post-stroke epilepsy: Retrospective analysis[J ] . Adv Clin Exp Med, 2021, 30(1): 29-34. DOI: 10.17219/acem/128745.
Mullen S A, Berkovic S F. Genetic generalized epilepsies[J]. Epilepsia, 2018, 59(6): 1148-1153. DOI: 10.1111/epi.14042.
GESCHE J, BEIER C P. Drug resistance in idiopathic generalized epilepsies: Evidence and concepts[J]. Epilepsia, 2022, 63(12): 3007-3019. DOI: 10.17219/acem/128745.
SUZUKI T, KOIKE Y, ASHIKAWA K, et al . Genome-wide association study of epilepsy in a Japanese population identified an associated region at chromosome 12q24[J ] . Epilepsia, 2021, 62(6): 1391-1400. DOI: 10.1111/epi.16911.
MATTISKE T, LEE K, GECZ J, et al . Embryonic forebrain transcriptome of mice with polyalanine expansion mutations in the ARX homeobox gene[J ] . Hum Mol Genet, 2016, 25(24): 5433-5443. DOI: 10.1093/hmg/ddw360.
CHANG R S, LEUNG W C, VASSALLO M, et al . Antiepileptic drugs for the primary and secondary prevention of seizures after stroke[J ] . Cochrane Database Syst Rev, 2022, 2(2): CD005398. DOI: 10.1002/14651858.CD005398.pub4.
PUNIA V, HONOMICHL R, CHANDAN P, et al . Long-term continuation of anti-seizure medications after acute stroke[J ] . Ann Clin Transl Neurol, 2021, 8(9): 1857-1866. DOI: 10.1002/acn3.51440.
MAYERHOFER E, PARODI L, NARASIMHALU K, et al . Genetic variation supports a causal role for valproate in prevention of ischemic stroke[J ] . Int J Stroke, 2024, 19(1): 84-93. DOI: 10.1177/17474930231190259.
0
浏览量
568
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621