| Title: | Adjusting for common variant polygenic scores improves yield in rare variant association analyses |
| Journal: | Nature Genetics |
| Published: | 23 Mar 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/36959364/ |
| DOI: | https://doi.org/10.1038/s41588-023-01342-w |
| URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11078202 |
| Citations: | 14 (14 in last 2 years) as of 8 Aug 2024 |
Publication 11232
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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 × 10−6), 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.</p>
6 Keywords
- Genome-Wide Association Study
- Models, Genetic
- Multifactorial Inheritance
- Phenotype
- Polymorphism, Single Nucleotide
- Quantitative Trait Loci
8 Authors
- Sean J. Jurgens
- James P. Pirruccello
- Seung Hoan Choi
- Valerie N. Morrill
- Mark Chaffin
- Steven A. Lubitz
- Kathryn L. Lunetta
- Patrick T. Ellinor
1 Application
| Application ID | Title |
|---|---|
| 17488 | Understanding the Genetic Basis of Cardiac Arrhythmias |
Enabling scientific discoveries that improve human health