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