Transcriptome wide association studies: general framework and methods

Background : Genome-wide association studies (GWAS) have succeeded in identifying tens of thousands of genetic variants associated with complex human traits during the past decade, however, they are still hampered by limited statistical power and dif fi culties in biological interpretation. With the recent progress in expression quantitative trait loci (eQTL) studies, transcriptome-wide association studies (TWAS) provide a framework to test for gene-trait associations by integrating information from GWAS and eQTL studies. Results : In this review, we will introduce the general framework of TWAS, the relevant resources, and the computational tools. Extensions of the original TWAS methods will also be discussed. Furthermore, we will brie fl y introduce methods that are closely related to TWAS, including MR-based methods and colocalization approaches. Connection and difference between these approaches will be discussed. Conclusion : Finally, we will summarize strengths, limitations, and potential directions for TWAS. Author summary: Transcriptome-wide association studies (TWAS) provide an important framework to test for gene-trait associations by integrating information from GWAS and eQTL studies. In this review, we systematically review the general framework and methods of transcriptome-wide association studies, and discuss their strengths, limitations, and potential future directions.