Evolving best practices for transcriptome-wide association studies accelerate discovery of gene-phenotype links

Transcriptome-wide association studies (TWAS) complement genome-wide association studies (GWAS) by using gene expression data to link specific genes to phenotypes. This review examines 37 TWAS studies across eight plant species, evaluating the impact of methodological choices on outcomes using maize and soybean datasets. Large sample sizes and synchronized sample collection for gene expression measurement appear to significantly increase power for discovering gene-phenotype linkages, while matching tissue, stage, and environment may matter much less than previously believed, making it feasible to reuse large and well-collected expression datasets across multiple studies. The development of statistical approaches and computational tools specifically optimized for plant TWAS data will ultimately be needed, but further potential remains to adapt advances developed in GWAS to TWAS contexts.