Adjusting for common variant polygenic scores improves yield in rare variant association analyses.

Nature genetics
Authors
Abstract

With the emergence of large-scale sequencing data, methods for improving power in rare variant association tests are needed. Here we show that adjusting for common variant polygenic scores improves yield in gene-based rare variant association tests across 65 quantitative traits in the UK Biobank (up to 20% increase at α = 2.6 × 10), without marked increases in false-positive rates or genomic inflation. Benefits were seen for various models, with the largest improvements seen for efficient sparse mixed-effects models. Our results illustrate how polygenic score adjustment can efficiently improve power in rare variant association discovery.

Year of Publication
2023
Journal
Nature genetics
Volume
55
Issue
4
Pages
544-548
Date Published
04/2023
ISSN
1546-1718
DOI
10.1038/s41588-023-01342-w
PubMed ID
36959364
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