Addressing overfitting bias due to sample overlap in polygenic risk scoring
Sample overlap between large Alzheimer's disease (AD) cohorts poses overfitting bias when using AD polygenic risk scores (PRSs). This study highlighted the effectiveness of overlap-adjusted PRS (OA -PRS) in mitigating overfitting and improving the accuracy of PRS estimations. New PRSs based on adjusted effect sizes showed increased power in association with clinical features.
Authors
- Sang‐Hyuk Jung (ORCID: https://orcid.org/0000-0003-4116-3327)
- Seung‐Geun Lee (ORCID: https://orcid.org/0000-0002-5205-3978)
- Andrew J. Saykin (ORCID: https://orcid.org/0000-0002-1376-8532)
- Christos A. Davatzikos (ORCID: https://orcid.org/0000-0002-1025-8561)
- Hong‐Hee Won (ORCID: https://orcid.org/0000-0001-5719-0552)
- Manu Shivakumar (ORCID: https://orcid.org/0000-0003-4733-7375)
- Dokyoon Kim (ORCID: https://orcid.org/0000-0002-4592-9564)
- Seokho Jeong (ORCID: https://orcid.org/0000-0002-1864-9962)
- Kwangsik Nho
- Young Jin Kim (ORCID: https://orcid.org/0000-0002-4900-9933)
- Li Shen (ORCID: https://orcid.org/0009-0003-0318-8328)
- Bong‐Jo Kim (ORCID: https://orcid.org/0000-0002-3722-2032)
- Heng Huang
- Paul M. Thompson
Institutions
- Seoul National University (KR)
- Kangwon National University (KR)
- University of Pittsburgh (US)
- Samsung Medical Center (KR)
- Korea National Institute of Health (KR)
- Imaging Center (US)
- Indiana University School of Medicine
- Indiana University – Purdue University Indianapolis (US)
- University of Pennsylvania (US)
- Sungkyunkwan University (KR)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2025-04-01
- DOI
- https://doi.org/10.1002/alz.70109
- Citations
- 3
- Primary Topic
- Genetic Associations and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 5.45
Funders
- Alzheimer's Disease Neuroimaging Initiative
- National Research Foundation
- National Research Foundation of Korea
- Ministry of Science and ICT, South Korea
- National Institutes of Health
- Centers for Disease Control and Prevention