United KingdomCommon gene-mapping method flips direction for 23% of plasma-protein genes.
Direction decides whether drug-target discovery should boost or block a gene.
Transcriptome-wide association studies infer gene activity from DNA variants, so researchers checked 1,543 proteins whose levels should rise with activity.
Filtering for shared causal variants helped, but gene-level false sign rates stayed above 10% at the strictest threshold.
The authors say the results raise questions about how these methods behave as commonly understood.
How each outlet framed it
- Nature
- explains that TWAS estimates the direction of gene effects, not just significance, and treats the misreading of that direction as the methods problem
Sources: Nature