Homomorphic Encryption: An Application to Polygenic Risk Scores

Abstract

Background: Polygenic risk scores (PRS) have emerged as a powerful tool in precision medicine, enabling personalized risk assessments for complex diseases. However, using sensitive genomic data in PRS calculations raises concerns about privacy and security. Fully Homomorphic Encryption (FHE) offers a promising solution by allowing computations on encrypted data, preserving the privacy of both genomic information and PRS models. Results: In this study, we present a novel application of FHE for secure and private PRS calculations using the CKKS protocol within the Lattigo library. Our approach involves a three-party system: clients (doctors with sensitive genetic data), modelers developing a PRS (academics or a company), and evaluators (a "local hospital" running the models while maintaining data confidentiality). We demonstrate the feasibility and accuracy of our protocol by applying it to synthetic datasets of various sizes and a robust 110k-SNP model for schizophrenia. The normal PRS calculation results are essentially identical to the encrypted calculation: between the two resultsR2is .999 & MSE is 2.27 times 10-6. Moreover, while the encrypted calculation is roughly 1000 times slower than conventional non-encrypted ones (when only considering the core PRS calculation), it is quite feasible on a single-CPU node - e.g. running on ≈ 1100 individuals with ≈ 110k SNPS took six minutes and ≈ 65G memory on a laptop computer. In addition, we investigate the impact of encryption parameters (modulus) on this computational time and accuracy in detail. Conclusion: By enabling secure PRS calculations on encrypted genomic data, our approach addresses the pressing need for privacy-preserving solutions in the era of precision medicine. The ability to perform accurate risk assessments while maintaining patient confidentiality paves the way for broader adoption of PRS and personalized medicine in healthcare, particularly with the advent of large-scale computing power.