{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:27:28Z","timestamp":1789658848265,"version":"4.0.1"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":14,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of General Medical Sciences of the National Institutes of Health","award":["R35GM155468"],"award-info":[{"award-number":["R35GM155468"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Polygenic risk scores (PRSs) aggregate genetic effect estimates to predict disease susceptibility, yet calculating one through an external service can require exposing raw genotype data. Homomorphic encryption hides those data during the calculation but, in prior work, still places a designated evaluator in a position of trust. We present bioETH-PRS, a protocol that replaces the evaluator with publicly auditable smart contracts on a blockchain supporting Fully Homomorphic Ethereum Virtual Machine (fhEVM). Using integer-exact encrypted arithmetic, bioETH-PRS computes the PRS dot product entirely in the encrypted domain, so genotype dosages and, at the model provider\u2019s discretion, the GWAS weights stay hidden from the parties performing the computation. A fixed-point encoding represents signed weights as nonnegative integers within a bound that rules out overflow, recovering the score to the precision of the published weights. A four-contract architecture separates data custody, model publication, computation, and output release, and supports both a classic path that stores encrypted inputs and an appreciably cheaper streaming path that discards them. A release oracle can return a randomized risk category instead of the raw score, limiting what a repeated querier learns. Prototype evaluation on real GWAS fixtures, including a run on a public testnet, shows cost growing linearly with variant count and suggests the approach may be practical where transaction fees are low. Trust is redistributed rather than removed: the system still depends on the contracts, the blockchain, and the fhEVM services. We evaluate additive models of moderate size, not genome-wide or clinical use.<\/jats:p>","DOI":"10.1093\/bib\/bbag503","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:19:37Z","timestamp":1788520777000},"source":"Crossref","is-referenced-by-count":0,"title":["bioETH-PRS: confidential polygenic risk scoring with smart contracts on an FHE-enabled blockchain"],"prefix":"10.1093","volume":"27","author":[{"given":"Kimon","family":"Antonios Provatas","sequence":"first","affiliation":[{"name":"Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute , Austin, TX 78712 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos","family":"Galanopoulos","sequence":"additional","affiliation":[{"name":"Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute , Austin, TX 78712 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilias","family":"Georgakopoulos-Soares","sequence":"additional","affiliation":[{"name":"Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute , Austin, TX 78712 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"2026091518012329200_ref1","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1001\/jamapsychiatry.2020.3049","article-title":"From basic science to clinical application of polygenic risk scores: a primer","volume":"78","author":"Wray","year":"2021","journal-title":"JAMA Psychiatry"},{"key":"2026091518012329200_ref2","doi-asserted-by":"publisher","first-page":"1883","DOI":"10.1016\/j.jacc.2018.07.079","article-title":"Genomic risk prediction of coronary artery disease in 480,000 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stronger","volume":"36","author":"Priv\u00e9","year":"2021","journal-title":"Bioinformatics."},{"key":"2026091518012329200_ref11","author":"Tune Insight SA"},{"key":"2026091518012329200_ref12","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1007\/s00145-019-09319-x","article-title":"TFHE: fast fully homomorphic encryption over the torus","volume":"33","author":"Chillotti","year":"2020","journal-title":"J Cryptol"},{"key":"2026091518012329200_ref13","author":"Zama"},{"key":"2026091518012329200_ref14","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.1186\/1472-6947-15-S5-S3","article-title":"Private genome analysis through homomorphic encryption","volume":"15","author":"Kim","year":"2015","journal-title":"BMC Med Inform Decis Mak"},{"key":"2026091518012329200_ref15","doi-asserted-by":"publisher","first-page":"11608","DOI":"10.1073\/pnas.1918257117","article-title":"Secure large-scale genome-wide association studies using homomorphic 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