Addressing overfitting bias due to sample overlap in polygenic risk scoring.

ABSTRACT:

Introduction

Numerous studies on Alzheimer's disease polygenic risk scores (PRSs) overlook sample overlap between International Genomics of Alzheimer's Project (IGAP) and target datasets like Alzheimer's Disease Neuroimaging Initiative (ADNI).

Methods

To address this, we developed overlap-adjusted PRS (OA PRS) and tested it on simulated data to assess biases from different scenarios by varying training, testing, and overlap proportions. OA PRS was used to adjust for sample bias in simulations; then, we applied OA PRS to IGAP and ADNI datasets and validated through visual diagnosis.

Results

OA PRS effectively adjusted for sample overlap in all simulation scenarios, as well as for IGAP and ADNI. The original IGAP PRS showed an inflated area under the receiver operating

SUBMITTER: Jeong S 

PROVIDER: S-EPMC11972974 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature