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Using External Reference Panel and Single-Variant Summary Statistics for Rare-Variant Aggregation Tests
Rare-variant aggregation tests are often used to increase the power to detect rare-variant associations, and can be performed using publicly available GWAS summary statistics. Accurate estimates of single-variant test statistic covariances are needed, but are often unavailable due to data size and inability to share individual-level genetic data. In this study we extend a previously proposed method of estimating covariance from an external reference panel to rare-variant aggregation tests. We apply our method to UK Biobank exome sequence data and observe squared Pearson correlation coefficients comparing aggregation test -log10(p-values) generated using individual-level data and UK Biobank external reference panels between 0.984 and 0.996 at a reference panel of 1,000 across multiple simulation settings. By using an African American reference panel (n=1,000) from the InPSYght study, we also show that our approach is robust to misspecification of the reference panel ancestry.
Date and Time
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Co-auteurs (non y compris vous-même)
Michael Boehnke
University of Michigan
Ryan Welch
University of Michigan
Christian Fuchsberger
Eurac Research
Langue de la présentation orale
Anglais
Langue des supports visuels
Anglais

Speaker

Edit Name Primary Affiliation
Brady Ryan University of Michigan