Nature GeneticsGenomicsPeer-reviewed journal article
Adjusting for Common Variant Polygenic Scores Improves Yield in Rare Variant Association Analyses
Sean Joseph JurgensiD, James P. PirruccelloiD, Seung Hoan ChoiiD, Valerie N. MorrilliD, Mark D. ChaffiniD, Steven A. LubitziD, Kathryn L. LunettaiD, Patrick T. EllinoriD
Abstract
With the emergence of large-scale sequencing data, methods for improving power in rare variant analyses (RVAT) are needed. Here, we show that adjusting for common variant polygenic scores improves the yield in gene-based RVAT across 65 quantitative traits in the UK Biobank (up to 20% increase at =2.6x10-6), without a marked increase in false-positive rates or genomic inflation. Our results illustrate how adjusting for common variant effects can aid in rare variant association discovery.
- organism: human
- assay: whole-exome sequencing
- research focus: variant effect prediction
- research focus: GWAS / association mapping
- approach: statistical model
- Citations
- 48
- FWCI
- 7.79
- Field percentile
- top 1%
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