Journal of Shandong University (Health Sciences) ›› 2025, Vol. 63 ›› Issue (9): 20-30.doi: 10.6040/j.issn.1671-7554.0.2024.1463

• Special Issue on “Big DataEnabled, AI Foundation ModelDriven Multimodal Cohort Design and Analysis” • Previous Articles    

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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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

CLC Number: 

  • R742.1
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