Homomorphic encryption enables privacy preserving polygenic risk scores.

Cell reports methods
Authors
Keywords
Abstract

Polygenic risk score models (PRSs) are important tools in precision medicine, enabling personalized risk prediction; however, they raise privacy concerns. Fully homomorphic encryption (FHE) provides a potential solution, allowing computation on encrypted genomic data. Here, we develop an open-source implementation of FHE for PRS (HEPRS), available online. HEPRS involves a three party system: clients (clinicians handling sensitive genetic data), modelers developing a PRS (academics), and evaluators (a local hospital running the models while maintaining confidentiality). We apply HEPRS to synthetic datasets and a 110,000 single-nucleotide-polymorphism (SNP) model for schizophrenia and show that encrypted and plaintext PRSs agree closely. We investigate encryption parameters that influence computational accuracy, memory, and time, demonstrating that HEPRS is practical to use on a single CPU. These results show that FHE enables realistic, privacy-preserving PRSs with negligible accuracy loss, supporting secure and scalable genomic analytics.

Year of Publication
2026
Journal
Cell reports methods
Pages
101271
Date Published
01/2026
ISSN
2667-2375
DOI
10.1016/j.crmeth.2025.101271
PubMed ID
41512862
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