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

A Arjhun Swaminathan A Anika Hannemann A Ali Burak Ünal N Nico Pfeifer M Mete Akgün

Abstract

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.

Article Details

Volume / Issue Vol. 16, Issue 1
Published December 09, 2025
ISSN 2041-1723
Publisher Nature Portfolio

Journal Info

Nature Communications

Nature Portfolio

ISSN: 2041-1723 Open Access Life Sciences

Authors (5)

A

Arjhun Swaminathan

A

Anika Hannemann

A

Ali Burak Ünal

N

Nico Pfeifer

M

Mete Akgün