Public platform with 39,472 exome control samples enables association studies without genotype sharing.

Nature genetics
Authors
Abstract

Acquiring a sufficiently powered cohort of control samples matched to a case sample can be time-consuming or, in some cases, impossible. Accordingly, an ability to leverage genetic data from control samples that were already collected elsewhere could dramatically improve power in genetic association studies. Sharing of control samples can pose significant challenges, since most human genetic data are subject to strict sharing regulations. Here, using the properties of singular value decomposition and subsampling algorithm, we developed a method allowing selection of the best-matching controls in an external pool of samples compliant with personal data protection and eliminating the need for genotype sharing. We provide access to a library of 39,472 exome sequencing controls at enabling association studies for case cohorts lacking control subjects. Using this approach, control sets can be selected from this online library with a prespecified matching accuracy, ensuring well-calibrated association analysis for both rare and common variants.

Year of Publication
2024
Journal
Nature genetics
Date Published
01/2024
ISSN
1546-1718
DOI
10.1038/s41588-023-01637-y
PubMed ID
38200129
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