Genome-wide association studies (GWAS) identify correlations between the genetic variants and an observable characteristic such as a disease. Previous works presented privacy-preserving distributed algorithms for a federation of genome data holders that spans multiple institutional and legislative domains to securely compute GWAS results. However, these algorithms have limited applicability, since they still require a centralized instance to operate on the data and decide whether GWAS results can be safely disclosed, which violates privacy regulations, such as GDPR. In this work, we introduce GenDPR, a distributed middleware that leverages Trusted Execution Environments (TEEs) to securely determine a subset of the potential GWAS statistics that can be safely released. GenDPR achieves the same accuracy as centralized solutions, but requires transferring significantly less data because TEEs only exchange intermediary results but no genomes. Additionally, GenDPR can be configured to tolerate all-but-one honest-but-curious federation members colluding with the aim to expose genomes of correct members. ... Read more

The popularization of large-scale federated Genome-Wide Association Study (GWAS) where multiple data owners share their genome data to conduct federated analytics uncovers new privacy issues that have remained unnoticed or not given proper attention. Indeed, as soon as a diverse type of interested parties (e.g., private or public biocenters and governmental institutions from around the globe) and individuals from heterogeneous populations are participating in cooperative studies, interdependent and multi-party privacy appear as crucial issues that are currently not adequately assessed. In fact, in federated GWAS environments, the privacy of individuals and parties does not depend solely on their own behavior anymore but also on others, because a collaborative environment opens new credible adversary models. For instance, one might want to tailor the privacy guarantees to withstand the presence of potentially colluding federation members aiming to violate other members’ data privacy and the privacy deterioration that might occur in the presence of interdependent genomic data (e.g., due to the presence of relatives in studies or the perpetuation of previous genomic privacy leaks in future studies). In this work, we catalog and discuss the features, unsolved problems, and challenges to tackle toward truly end-to-end private and practical federated GWAS. ... Read more

Genome-wide Association Studies (GWASes) identify genomic variations that are statistically associated with a trait, such as a disease, in a group of individuals. Unfortunately, careless sharing of GWAS statistics might give rise to privacy attacks. Several works attempted to reconcile secure processing with privacy-preserving releases of GWASes. However, we highlight that these approaches remain vulnerable if GWASes utilize overlapping sets of individuals and genomic variations. In such conditions, we show that even when relying on state-of-the-art techniques for protecting releases, an adversary could reconstruct the genomic variations of up to 28.6% of participants, and that the released statistics of up to 92.3% of the genomic variations would enable membership inference attacks. We introduce I-GWAS, a novel framework that securely computes and releases the results of multiple possibly interdependent GWASes. I-GWAScontinuously releases privacy-preserving and noise-free GWAS results as new genomes become available. ... Read more

Genome-Wide Association Studies (GWAS) identify the genomic variations that are statistically associated with a particular phenotype (e.g., a disease). The confidence in GWAS results increases with the number of genomes analyzed, which encourages federated computations where biocenters would periodically share the genomes they have sequenced. However, for economical and legal reasons, this collaboration will only happen if biocenters cannot learn each others’ data. In addition, GWAS releases should not jeopardize the privacy of the individuals whose genomes are used. We introduce DyPS, a novel framework to conduct dynamic privacy-preserving federated GWAS. DyPS leverages a Trusted Execution Environment to secure dynamic GWAS computations. Moreover, DyPS uses a scaling mechanism to speed up the releases of GWAS results according to the evolving number of genomes used in the study, even if individuals retract their participation consent. Lastly, DyPS also tolerates up to all-but-one colluding biocenters without privacy leaks. We implemented and extensively evaluated DyPS through several scenarios involving more than 6 million simulated genomes and up to 35,000 real genomes. Our evaluation shows that DyPS updates test statistics with a reasonable additional request processing delay (11% longer) compared to an approach that would update them with minimal delay but would lead to 8% of the genomes not being protected. In addition, DyPS can result in the same amount of aggregate statistics as a static release (i.e., at the end of the study), but can produce up to 2.6 times more statistics information during earlier dynamic releases. Besides, we show that DyPS can support a larger number of genomes and SNP positions without any significant performance penalty. ... Read more