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Private Genomes and Public SNPs: Homomorphic Encryption of Genotypes and Phenotypes for Shared Quantitative Genetics

Mott, R; Fischer, C; Prins, P; Davies, RW; (2020) Private Genomes and Public SNPs: Homomorphic Encryption of Genotypes and Phenotypes for Shared Quantitative Genetics. Genetics , 215 (2) pp. 359-372. 10.1534/genetics.120.303153. Green open access

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Abstract

Sharing human genotype and phenotype data is essential in order to discover otherwise inaccessible genetic associations but is a challenge because of privacy concerns. Here we present a method of homomorphic encryption that obscures individuals' genotypes and phenotypes and is suited to quantitative genetic association analysis. Encrypted ciphertext and unencrypted plaintext are analytically interchangeable. The encryption uses a high-dimensional random linear orthogonal transformation key that leaves the likelihood of quantitative trait data unchanged under a linear model with normally distributed errors. It also preserves linkage disequilibrium between genetic variants and associations between variants and phenotypes. It scrambles relationships between individuals: encrypted genotype dosages closely resemble Gaussian deviates, and can be replaced by quantiles from a Gaussian with negligible effects on accuracy. Likelihood-based inferences are unaffected by orthogonal encryption. These include linear mixed models to control for unequal relatedness between individuals, heritability estimation, and including covariates when testing association. Orthogonal transformations can be applied in a modular fashion for multi-party federated mega-analyses where the parties first agree to share a common set of genotype sites and covariates prior to encryption. Each then privately encrypts and shares their own ciphertext, and analyses all parties' ciphertexts. In the absence of private variants, or knowledge of the key, we show that it is infeasible to decrypt ciphertext using existing brute-force or noise reduction attacks. We present the method as a challenge to the community to determine its security.

Type: Article
Title: Private Genomes and Public SNPs: Homomorphic Encryption of Genotypes and Phenotypes for Shared Quantitative Genetics
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1534/genetics.120.303153
Publisher version: https://doi.org/10.1534/genetics.120.303153
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: genetic privacy, homomorphic encryption, quantitative genetics
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: https://discovery.ucl.ac.uk/id/eprint/10096460
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