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山东大学学报 (医学版) ›› 2025, Vol. 63 ›› Issue (9): 20-30.doi: 10.6040/j.issn.1671-7554.0.2024.1463

• “大数据赋能AI大模型驱动的多模态队列设计与分析”重点专题 • 上一篇    

虚弱和癫痫关联研究:前瞻性队列和孟德尔随机化分析

王乐1,2,罗清馨1,2,吴思佳1,2,吴雨桐1,2,葛祎蕾1,2,俞一凡1,2,韦云1,2,吉寒冰1,2,刘铁梅1,2,张紫妍1,2,修佳伟1,2,薛付忠1,2,3,李洪凯1,2   

  1. 1.山东大学齐鲁医学院公共卫生学院医学数据学系, 山东 济南 250012;2.国家健康医疗大数据研究院, 山东 济南 250003;3.山东大学齐鲁医院, 山东 济南 250012
  • 发布日期:2025-09-08
  • 通讯作者: 李洪凯. E-mail:lihongkaiyouxiang@163.com薛付忠. E-mail:xuefzh@sdu.edu.cn
  • 基金资助:
    国家重点研发计划(2022YFC3502100);国家自然科学基金面上项目(82173625);国家自然科学基金重点项目(82330108);山东省重点研发计划(2024CXPT085);2021年山东省医学会临床研究基金-齐鲁专项(YXH2022DZX02008);河南省重大科技专项项目(241100310300)

Associations between frailty and the risk of epilepsy: a prospective cohort study and Mendelian randomization analysis

WANG Le1,2, LUO Qingxin1,2, WU Sijia1,2, WU Yutong1,2, GE Yilei1,2, YU Yifan1,2, WEI Yun1,2, JI Hanbing1,2, LIU Tiemei1,2, ZHANG Ziyan1,2, XIU Jiawei1,2, XUE Fuzhong1,2,3, LI Hongkai1,2   

  1. 1. Department of Medical Dataology, School of Public Health, Qilu Medical College, Shandong University, Jinan 250012, Shandong, China;
    2. National Institute of Health and Medicine Big Data, Shandong University, Jinan 250003, Shandong, China;
    3. Qilu Hospital of Shandong University, Jinan 250012, Shandong, China
  • Published:2025-09-08

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摘要： 目的 基于英国生物样本库(UK Biobank, UKB)数据,探讨身体虚弱与癫痫发病风险的关联。 方法 从UKB数据库筛选出368 857例目标人群,在2006年至2020年基线调查时收集体质量减轻、疲惫频率、无力、缺乏身体活动和走路速度慢等5项暴露信息,获得随访期间的新发癫痫事件,并调整基线调查时年龄、性别、种族、受教育程度、家庭平均年收入、吸烟状况、饮酒状况、脑血管疾病、痴呆、头部受伤、脑部感染、酒精相关疾病等混杂因素。采用COX比例风险模型计算虚弱表型与癫痫关联的风险比(hazard ratio, HR)及95%置信区间(confidence interval, CI),并以倾向性得分匹配作为补充性分析。同时,使用全基因组关联研究(genome-wide association study, GWAS)数据筛选遗传工具变量(instrument variables, IVs),进行孟德尔随机化分析(Mendelian randomization, MR),包括逆方差加权(inverse variance weighted, IVW)法、MR-Egger法、加权中位数(weighted median, WME)法、简单模式(simple mode, SM)法和加权模式(weighted mode, WM)法,敏感性分析验证结果的稳健性。 结果 调整可能的混杂因素后,队列分析结果显示身体虚弱与癫痫发病风险之间存在显著关联,HR(95%CI)为1.72(1.44~2.05),P<0.001;匹配后的结果与主分析基本一致。MR结果中IVW法(OR=1.99, 95%CI: 1.21~3.28, P=0.007)和WME法(OR=2.24, 95%CI: 1.12~4.46, P=0.022)结果均表明遗传决定的虚弱指数与癫痫风险呈正相关,敏感性分析证明结果不存在异质性和水平多效性。 结论 身体虚弱可能是癫痫的风险因素,此结论有助于探讨癫痫病因及发病机制,为癫痫的临床治疗方案和预防策略提供数据支撑。

关键词: 癫痫, 虚弱, 队列研究, 孟德尔随机化

Abstract: Objective To evaluate the associations between physical frailty and the risk of epilepsy based on the UK Biobank(UKB)database. Methods A total of 368,857 target participants were selected from the UKB database. Five exposures from the baseline data were collected from 2006 to 2020, which included weight loss, exhaustion frequency, weakness, physical inactivity and slow walking speed. New epilepsy incidents during the follow-up period were further obtained. COX proportional hazards regression models were applied to evaluate the hazard ratio(HR)and 95% confidence interval(CI)of frailty phenotype with the risk of epilepsy after adjusting for age, gender, race, education level, family income, smoking status, alcohol status, cerebrovascular diseases, dementia, head injuries, brain infections and alcohol-related disorders at baseline. Propensity score matching was applied as supplementary analysis. Mendelian randomization(MR)analysis was conducted using genetic instrumental variables(IVs)selected from genome-wide association study(GWAS)data, including inverse variance-weighting(IVW)method, MR-Egger method, weighted median(WME)method, simple mode(SM)method and weighted mode(WM)method. Sensitivity analysis was performed to verify the robustness of results. Results The cohort analysis revealed a significant association between physical frailty and the risk of epilepsy after adjustment for potential confounding, with an HR(95%CI)of 1.72(1.44-2.05), P<0.001. Results after matching were consistent with the main analysis. IVW method(OR=1.99, 95%CI: 1.21-3.28, P=0.007)and WME method(OR=2.24, 95%CI: 1.12-4.46, P=0.022)indicated a positive correction between genetically determined frailty index and epilepsy risk. Sensitivity analysis confirmed the absence of heterogeneity and horizontal pleiotropy. Conclusion Physical frailty may contribute to the development of epilepsy. These results help to explore the etiology and pathogenesis of epilepsy, and provide evidence for clinical epilepsy treatment and prevention strategies.

Key words: Epilepsy, Frailty, Cohort studies, Mendelian randomization

中图分类号: 

  • R742.1
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