A resampling-based approach to share reference panels

For many genome-wide association studies, imputing genotypes from a haplotype reference panel is a necessary step. Over the past 15 years, reference panels have become larger and more diverse, leading to improvements in imputation accuracy. However, the latest generation of reference panels is subject to restrictions on data sharing due to concerns about privacy, limiting their usefulness for genotype imputation. In this context, we propose RESHAPE, a method that employs a recombination Poisson process on a reference panel to simulate the genomes of hypothetical descendants after multiple generations. This data transformation helps to protect against re-identification threats and preserves important data attributes, such as linkage disequilibrium (LD) patterns and, to some degree, Identity-By-Descent (IBD) sharing, allowing for genotype imputation. Our experiments on gold standard datasets show that simulated descendants up to eight generations can serve as reference panels without significantly reducing genotype imputation accuracy. We suggest that this specific type of data anonymization could be used to generate synthetic reference panels available under less restrictive data sharing policies. ### Competing Interest Statement The authors have declared no competing interest.