GOPHER: Optimization-based Phenotype Randomization for Genome-Wide Association Studies with Differential Privacy

Fuente: arXiv
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Main Authors: Nandi, Anupama, Neel, Seth, Cho, Hyunghoon
Format: Preprint
Published: 2025
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author Nandi, Anupama
Neel, Seth
Cho, Hyunghoon
author_facet Nandi, Anupama
Neel, Seth
Cho, Hyunghoon
contents Genome-wide association studies (GWAS) are an essential tool in biomedical research for identifying genetic factors linked to health and disease. However, publicly releasing GWAS summary statistics poses well-recognized privacy risks, including the potential to infer an individual's participation in the study or to reveal sensitive phenotypic information (e.g., disease status). While differential privacy (DP) offers a rigorous mathematical framework for mitigating these risks, existing DP techniques for GWAS either introduce excessive noise or restrict the release to a limited set of results. In this work, we present practical DP mechanisms for releasing the complete set of genome-wide association statistics with privacy guarantees. We demonstrate the accuracy of the privacy-preserving statistics released by our mechanisms on a range of GWAS datasets from the UK Biobank, utilizing both real and simulated phenotypes. We introduce two key techniques to overcome the limitations of prior approaches: (1) an optimization-based randomization mechanism that directly minimizes the expected error in GWAS results to enhance utility, and (2) the use of personalized priors, derived from predictive models privately trained on a subset of the dataset, to enable sample-specific optimization which further reduces the amount of noise introduced by DP. Overall, our work provides practical tools for accurately releasing comprehensive GWAS results with provable protection of study participants.
format Preprint
id arxiv_https___arxiv_org_abs_2512_04225
institution arXiv
publishDate 2025
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spellingShingle GOPHER: Optimization-based Phenotype Randomization for Genome-Wide Association Studies with Differential Privacy
Nandi, Anupama
Neel, Seth
Cho, Hyunghoon
Quantitative Methods
Genome-wide association studies (GWAS) are an essential tool in biomedical research for identifying genetic factors linked to health and disease. However, publicly releasing GWAS summary statistics poses well-recognized privacy risks, including the potential to infer an individual's participation in the study or to reveal sensitive phenotypic information (e.g., disease status). While differential privacy (DP) offers a rigorous mathematical framework for mitigating these risks, existing DP techniques for GWAS either introduce excessive noise or restrict the release to a limited set of results. In this work, we present practical DP mechanisms for releasing the complete set of genome-wide association statistics with privacy guarantees. We demonstrate the accuracy of the privacy-preserving statistics released by our mechanisms on a range of GWAS datasets from the UK Biobank, utilizing both real and simulated phenotypes. We introduce two key techniques to overcome the limitations of prior approaches: (1) an optimization-based randomization mechanism that directly minimizes the expected error in GWAS results to enhance utility, and (2) the use of personalized priors, derived from predictive models privately trained on a subset of the dataset, to enable sample-specific optimization which further reduces the amount of noise introduced by DP. Overall, our work provides practical tools for accurately releasing comprehensive GWAS results with provable protection of study participants.
title GOPHER: Optimization-based Phenotype Randomization for Genome-Wide Association Studies with Differential Privacy
topic Quantitative Methods
url https://arxiv.org/abs/2512.04225