Confidential computing for population-scale genome-wide association studies with SECRET-GWAS

Genomic data from a single institution lacks global diversity representation, especially for rare variants and diseases. Confidential computing can enable collaborative genome-wide association studies (GWAS) without compromising privacy or accuracy. However, due to limited secure memory space and performance overheads, previous solutions fail to support widely used regression methods. Here we present SECRET-GWAS—a rapid, privacy-preserving, population-scale, collaborative GWAS tool. We discuss several system optimizations, including streaming, batching, data parallelization and reducing trusted hardware overheads to efficiently scale linear and logistic regression to over a thousand processor cores on an Intel SGX-based cloud platform. In addition, we protect SECRET-GWAS against several hardware side-channel attacks. SECRET-GWAS is an open-source tool and works with the widely used Hail genomic analysis framework. Our experiments on Azure’s Confidential Computing platform demonstrate that SECRET-GWAS enables multivariate linear and logistic regression GWAS queries on population-scale datasets from ten independent sources in just 4.5 and 29 minutes, respectively. Secure collaborative genome-wide association studies (GWAS) with population-scale datasets address gaps in genomic data. This work proposes SECRET-GWAS and system optimizations that overcome resource constraints and exploit parallelism, while maintaining privacy and accuracy.