ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025
Addressing overfitting bias due to sample overlap in polygenic risk scoring.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
6 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Development and validation of a multiancestry and multitrait polygenic risk score for lung cancer.Nature communications · 2026Pooled it
- Predictive Value of Machine Learning for Poststroke Mortality Risk: Systematic Review and Meta-Analysis.Journal of medical Internet research · 2026Pooled it
- Groundwater quality and hypertension in India: addressing misclassification and predictive accuracy in Biswas et al.Journal of exposure science & environmental epidemiology · 2026Article
- Methods for modeling gene-environment interplay using polygenic risk scores.Statistical applications in genetics and molecular biology · 2026Review
- Understanding the alcohol harm paradox: A multivariable mendelian randomization approach.PLoS genetics · 2025Article
- Addressing overfitting bias due to sample overlap in polygenic risk scoring.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
Abstract
introductionNumerous 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).
methodsTo 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.
resultsOA 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 characteristic (AUROC: 0.915) on overlapping samples. OA PRS reduced the AUROC to 0.726, closely aligning with the AUROC of non-overlapping samples (0.712). Further, visual diagnostics confirmed the effectiveness of our adjustments. DISCUSSION: With OA PRS, we were able to adjust the IGAP summary-based PRS for the overlapped ADNI samples, allowing the dataset to be fully used without the risk of overfitting. HIGHLIGHTS: 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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.