Variability in epilepsy polygenic risk prediction across Taiwanese population and clinical cohorts

OBJECTIVE: This study was undertaken to evaluate the predictive, stratification, and prognostic utility of polygenic risk scores (PRSs) for epilepsy in three Taiwanese cohorts comprising more than 7000 cases among more than 600 000 individuals, thereby addressing the limited evidence on PRS performance in non-European populations. METHODS: Leveraging results from the latest multiancestry genome-wide association study (GWAS), we calculated PRS for all epilepsy, genetic generalized epilepsy (GGE), and focal epilepsy (FE) in two population cohorts-Taiwan Biobank-National Health Insurance Research Database (TWB-NHIRD; N ~ 105 K) and Taiwan Precision Medicine Initiative (TPMI; N ~ 500 K), with cases defined by International Classification of Diseases codes and medications-and a clinically ascertained sample (Taiwanese subset of the Epi25 consortium [Epi25-TWN]; N = 1140). PRS performance was assessed through lifetime risk models, age-at-onset stratifications, and phenome-wide association studies (PheWASs). RESULTS: = .14%-.22%). FE PRS effects on FE were more consistent but modest (ORs = 1.02-1.16 [95% CI = .97-1.33]). No prognostic value of PRS was found in predicting epilepsy from syncope or unspecified seizures. Individuals in the top 5% GGE PRS had >4-fold increased risk in Epi25-TWN but <1.5-fold in the others. Restricting to earlier onset cases strengthened PRS signals in population cohorts, particularly for GGE, with PheWAS analysis revealing epilepsy-specific associations. PRS effects were generally comparable but attenuated relative to European studies. SIGNIFICANCE: Cohort design and phenotyping accuracy strongly influence the assessment of the predictive value of epilepsy PRS, highlighting caution in clinical interpretation. Incorporating richer phenotypic data and more diverse GWASs will be crucial to enhancing its applicability and clinical potential.

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Publication Details

Journal
Epilepsia
Published
2026-06-25
DOI
https://doi.org/10.1002/epi.70353
Primary Topic
Genetic Associations and Epidemiology
Type
article
Field-Weighted Citation Impact
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article

Variability in epilepsy polygenic risk prediction across Taiwanese population and clinical cohorts

Yen‐Chen Anne Feng, Ming-Yuh Chang, Remi Stevelink, Chen-Jui Ho et al.
Epilepsia
Genetic Associations and Epidemiology
article

Variability in epilepsy polygenic risk prediction across Taiwanese population and clinical cohorts

Yen‐Chen Anne Feng, Ming-Yuh Chang, Remi Stevelink, Chen-Jui Ho, Paul Chih-Hsueh Chen, Tsong‐Hai Lee, Shun‐Fa Yang, Jen-Tse Chen, Wei-Ming Cheng, Chung‐Yao Hsu, Che-Cheng Chang, Tso‐Fu Wang, Chin‐Hsien Lin, Sheng‐Feng Sung, Lung Chan, Mei‐Ching Lee, Jiann‐Shing Jeng, Fu‐Chi Yang, Yung-Chuan Huang, Meng‐Han Tsai, Saint Shiou-Sheng Chen, Yo‐Tsen Liu, Shinn‐Zong Lin, Hsin Tung, Yueh‐Feng Sung, Sung‐Hui Tseng, Hung‐Hsin Chen, Chih-Kuang Cheng, Ming Chen, Siwei Chen, Yuan‐Han Yang, Tzu‐Hung Hsiao, Yu-Cheng Chu, Che-Yu Chou, Yu-Hsiang Su, S. Lee, Ying‐Chi Fan, Yuan‐Hung Liu, Yi‐Syuan Ke
article en

Abstract

OBJECTIVE: This study was undertaken to evaluate the predictive, stratification, and prognostic utility of polygenic risk scores (PRSs) for epilepsy in three Taiwanese cohorts comprising more than 7000 cases among more than 600 000 individuals, thereby addressing the limited evidence on PRS performance in non-European populations. METHODS: Leveraging results from the latest multiancestry genome-wide association study (GWAS), we calculated PRS for all epilepsy, genetic generalized epilepsy (GGE), and focal epilepsy (FE) in two population cohorts-Taiwan Biobank-National Health Insurance Research Database (TWB-NHIRD; N ~ 105 K) and Taiwan Precision Medicine Initiative (TPMI; N ~ 500 K), with cases defined by International Classification of Diseases codes and medications-and a clinically ascertained sample (Taiwanese subset of the Epi25 consortium [Epi25-TWN]; N = 1140). PRS performance was assessed through lifetime risk models, age-at-onset stratifications, and phenome-wide association studies (PheWASs). RESULTS: = .14%-.22%). FE PRS effects on FE were more consistent but modest (ORs = 1.02-1.16 [95% CI = .97-1.33]). No prognostic value of PRS was found in predicting epilepsy from syncope or unspecified seizures. Individuals in the top 5% GGE PRS had >4-fold increased risk in Epi25-TWN but <1.5-fold in the others. Restricting to earlier onset cases strengthened PRS signals in population cohorts, particularly for GGE, with PheWAS analysis revealing epilepsy-specific associations. PRS effects were generally comparable but attenuated relative to European studies. SIGNIFICANCE: Cohort design and phenotyping accuracy strongly influence the assessment of the predictive value of epilepsy PRS, highlighting caution in clinical interpretation. Incorporating richer phenotypic data and more diverse GWASs will be crucial to enhancing its applicability and clinical potential.

Epilepsia
Fu Jen Catholic University (TW), National Sun Yat-sen University (TW), National Yang Ming Chiao Tung University (TW), Kaohsiung Medical University (TW), National Chung Hsing University (TW), National Taiwan University (TW), Chang Gung University (TW), National Taipei University of Nursing and Health Science (TW), Utrecht University (NL), University of Taipei (TW), Tzu Chi Foundation (TW), Taipei Medical University Hospital (TW), Kaohsiung Medical University Chung-Ho Memorial Hospital (TW), Taipei Veterans General Hospital (TW), University Medical Center Utrecht (NL), University of Chicago (US), Taichung Veterans General Hospital (TW), Kaohsiung Chang Gung Memorial Hospital (TW), Institute of Biomedical Sciences, Academia Sinica (TW), Far Eastern Memorial Hospital (TW), Chung Shan Medical University Hospital (TW), Chia-Yi Christian Hospital (TW), Linkou Chang Gung Memorial Hospital (TW), Taipei City Hospital (TW), Cathay General Hospital (TW), National Taiwan University Hospital (TW), Koo Foundation Sun Yat-Sen Cancer Center (TW), Taipei Medical University-Shuang Ho Hospital (TW), Changhua Christian Hospital (TW), Taipei Medical University (TW), National Defense Medical Center (TW), Chung Shan Medical University (TW)
Chang Gung Memorial Hospital, National Health Research Institutes, Taipei Veterans General Hospital
Openalex Percentile: Top 7%
Genetic Associations and Epidemiology
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