TWAS gets gene effect direction wrong 23-33% of the time, Nature Genetics study finds
anshulkundaje · x · 2026-10-30
A Nature Genetics paper from Pritchard lab (Stanford) stress-tests how accurately TWAS infers a gene's direction of effect on a trait. Using plasma proteins (higher expression should raise protein levels) and loss-of-function burden tests for complex traits as ground-truth expectations, they measure false sign rates of 23% for proteins and 33% for complex traits, attributing much of the discordance to cases where expression and protein regulation diverge.
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