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Article

A gene-specific variance-control approach corrects polygenicity-driven inflation observed in transcriptome-wide association studies.

American journal of human genetics - 5 Feb 2026

Liang Yanyu, Nyasimi Festus, Im Hae Kyung

Abstract excerpt

Transcriptome-wide association studies (TWASs) and related methods (xWASs) have been widely adopted in genetic studies to understand molecular traits as mediators between genetic variation and disease. However, the effect of polygenicity on the validity of these mediator-trait association tests has largely been overlooked. Given the widespread polygenicity of complex traits, it is necessary to assess the accuracy...

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Identifiers

PMID: 41564881
DOI: 10.1016/j.ajhg.2025.12.014
PMCID: PMC13087401

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