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 α=2.6×10−6), 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.
Competing Interest Statement
P.T.E. has received sponsored research support from Bayer AG and IBM Health, and he has consulted for Bayer AG, Novartis and MyoKardia. S.A.L. receives sponsored research support from Bristol Myers Squibb / Pfizer, Bayer AG, Boehringer Ingelheim, Fitbit, and IBM, and has consulted for Bristol Myers Squibb / Pfizer, Bayer AG, and Blackstone Life Sciences.