bioETH-PRS: Confidential Polygenic Risk Scoring without a Trusted Evaluator via Fully Homomorphic Encryption on a Programmable Blockchain
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arXiv
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| Natura: | Preprint |
| Pubblicazione: |
2026
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| author | Provatas, Kimon Antonios Galanopoulos, Christos Georgakopoulos-Soares, Ilias |
| author_facet | Provatas, Kimon Antonios Galanopoulos, Christos Georgakopoulos-Soares, Ilias |
| contents | Polygenic risk scores (PRSs) aggregate genetic effect estimates to predict disease susceptibility, yet clinical deployment often exposes raw genotype data to third-party compute infrastructure. Prior homomorphic-encryption approaches, still require trust in a designated evaluator. We present bioETH-PRS, a protocol that replaces that evaluator role with immutable smart contracts on a blockchain supporting Fully Homomorphic Encryption (fhEVM). Using the integer-exact TFHE scheme, bioETH-PRS computes the PRS dot product entirely within the encrypted domain, keeping both genotype dosage vectors and GWAS weight vectors hidden from external parties throughout execution. We introduce a three-step fixed-point quantisation scheme for representing signed GWAS weights as unsigned 64-bit integers, achieving machine-epsilon reconstruction accuracy on validated fixtures. A four-contract architecture separates data custody, model publication, computation, and output release, and supports both a classic chunked path and a streaming path, with the latter reducing mock-measured gas by 37%. An on-chain noisy output oracle emits an encrypted noisy-score handle and a publicly decryptable ternary category, reducing raw score exposure and probing risk. Prototype evaluation on real GWAS fixtures confirms linear gas scaling and suggests that the approach may be cost-competitive in low-gas deployment environments. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2605_21634 |
| institution | arXiv |
| publishDate | 2026 |
| record_format | arxiv |
| spellingShingle | bioETH-PRS: Confidential Polygenic Risk Scoring without a Trusted Evaluator via Fully Homomorphic Encryption on a Programmable Blockchain Provatas, Kimon Antonios Galanopoulos, Christos Georgakopoulos-Soares, Ilias Genomics Polygenic risk scores (PRSs) aggregate genetic effect estimates to predict disease susceptibility, yet clinical deployment often exposes raw genotype data to third-party compute infrastructure. Prior homomorphic-encryption approaches, still require trust in a designated evaluator. We present bioETH-PRS, a protocol that replaces that evaluator role with immutable smart contracts on a blockchain supporting Fully Homomorphic Encryption (fhEVM). Using the integer-exact TFHE scheme, bioETH-PRS computes the PRS dot product entirely within the encrypted domain, keeping both genotype dosage vectors and GWAS weight vectors hidden from external parties throughout execution. We introduce a three-step fixed-point quantisation scheme for representing signed GWAS weights as unsigned 64-bit integers, achieving machine-epsilon reconstruction accuracy on validated fixtures. A four-contract architecture separates data custody, model publication, computation, and output release, and supports both a classic chunked path and a streaming path, with the latter reducing mock-measured gas by 37%. An on-chain noisy output oracle emits an encrypted noisy-score handle and a publicly decryptable ternary category, reducing raw score exposure and probing risk. Prototype evaluation on real GWAS fixtures confirms linear gas scaling and suggests that the approach may be cost-competitive in low-gas deployment environments. |
| title | bioETH-PRS: Confidential Polygenic Risk Scoring without a Trusted Evaluator via Fully Homomorphic Encryption on a Programmable Blockchain |
| topic | Genomics |
| url | https://arxiv.org/abs/2605.21634 |