Gene expression data provide molecular insights into the functional impact of genetic variation, for example, through expression quantitative trait loci (eQTLs). With an improving understanding of the association between genotypes and gene expression comes a greater concern that gene expression profiles could be matched to genotype profiles of the same individuals in another data set, known as a linking attack. Prior works show such a risk could analyze only a fraction of eQTLs that is independent owing to restrictive model assumptions, leaving the full extent of this risk incompletely understood. To address this challenge, we introduce the discriminative sequence model (DSM), a novel probabilistic framework for predicting a sequence of genotypes based on gene expression data. By modeling the joint distribution over all known eQTLs in a genomic region, DSM improves the power of linking attacks with necessary calibration for linkage disequilibrium and redundant predictive signals. We show greater linking accuracy of DSM compared with existing approaches across a range of attack scenarios and data sets including up to 22,288 individuals, suggesting that DSM helps uncover a substantial additional risk overlooked by previous studies. Our work provides a unified framework for assessing the privacy risks of sharing diverse omics data sets beyond transcriptomics.
© 2023 Sadhuka et al.; Published by Cold Spring Harbor Laboratory Press.