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PP-GWAS: Privacy Preserving Multi-Site Genome-wide Association Studies

Author

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  • Arjhun Swaminathan

    (University of Tübingen, Medical Data Privacy and Privacy-preserving Machine Learning (MDPPML)
    University of Tübingen, Institute for Bioinformatics and Medical Informatics (IBMI))

  • Anika Hannemann

    (Leipzig University, Dept. of Computer Science
    Center for Scalable Data Analytics and Artificial Intelligence (ScaDS.AI) Dresden/Leipzig
    School of Engineering, Zurich University of Applied Sciences)

  • Ali Burak Ünal

    (University of Tübingen, Medical Data Privacy and Privacy-preserving Machine Learning (MDPPML)
    University of Tübingen, Institute for Bioinformatics and Medical Informatics (IBMI)
    Delft University of Technology, Intelligent Vehicles Lab)

  • Nico Pfeifer

    (University of Tübingen, Institute for Bioinformatics and Medical Informatics (IBMI)
    University of Tübingen, Methods in Medical Informatics)

  • Mete Akgün

    (University of Tübingen, Medical Data Privacy and Privacy-preserving Machine Learning (MDPPML)
    University of Tübingen, Institute for Bioinformatics and Medical Informatics (IBMI))

Abstract

Genome-wide association studies help uncover genetic influences on complex traits and diseases. Importantly, multi-site data collaborations enhance the statistical power of these studies but pose challenges due to the sensitivity of genomic data. Existing privacy-preserving approaches to performing multi-site genome-wide association studies rely on computationally expensive cryptographic techniques, which limit applicability. To address this, we present PP-GWAS, a privacy-preserving algorithm that improves efficiency and scalability while maintaining data privacy. Our method leverages randomized encoding within a distributed framework to perform stacked ridge regression on a linear mixed model, enabling robust analysis of quantitative phenotypes. We show experimentally using real-world and synthetic data that our approach achieves twice the computational speed of comparable methods while reducing resource consumption.

Suggested Citation

  • Arjhun Swaminathan & Anika Hannemann & Ali Burak Ünal & Nico Pfeifer & Mete Akgün, 2025. "PP-GWAS: Privacy Preserving Multi-Site Genome-wide Association Studies," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-66771-z
    DOI: 10.1038/s41467-025-66771-z
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