Transcriptome-wide association studies often get effect direction wrong

A study by Peter A. Gerlach, published in Nature Genetics on 22 October 2026, reports that transcriptome-wide association studies frequently show a direction of effect that is reversed relative to the true underlying biological mechanism. This means results that appear significant may point the opposite way from what actually happens biologically, inflating false sign rates. The finding matters because such studies are widely used to link genetic variation to gene expression and disease. The author cautions researchers to take care when interpreting TWAS results and when applying them downstream, for example in target prioritization and follow-up functional work. Open questions include how pervasive the reversal problem is across tissues, methods and traits, and what corrections or safeguards should be adopted before TWAS findings are used in drug discovery or clinical interpretation.

Written by a model from the reports · updated 2 hours ago