Secure and Federated Genome-Wide Association Studies for Biobank-Scale Datasets

Abstract

Sharing data across institutions for genome-wide association studies (GWAS) would enhance the discovery of genetic variants linked to health and disease1, 2. However, existing data sharing regulations limit the scope of such collaborations3. Although cryptographic tools for secure computation promise to enable collaborative analysis with formal privacy guarantees, existing approaches either are computationally impractical or support only simplified analyses4-7. We introduce secure federated genome-wide association studies (SF-GWAS), a novel combination of secure computation frameworks and distributed algorithms that empowers efficient and accurate GWAS on private data held by multiple entities while ensuring data confidentiality. SF-GWAS supports the most widely-used GWAS pipelines based on principal component analysis (PCA) or linear mixed models (LMMs). We demonstrate the accuracy and practical runtimes of SF-GWAS on five datasets, including a large UK Biobank cohort of 410K individuals, showcasing an order-of-magnitude improvement in runtime compared to previous work. Our work realizes the power of secure collaborative genomic studies at unprecedented scale.