SR-TWAS: leveraging multiple reference panels to improve transcriptome-wide association study power by ensemble machine learning.

Multiple reference panels of a given tissue or multiple tissues often exist, and multiple regression methods could be used for training gene expression imputation models for transcriptome-wide association studies (TWAS). To leverage expression imputation models (i.e.

Omnibus proteome-wide association study identifies 43 risk genes for Alzheimer disease dementia.

Transcriptome-wide association study (TWAS) tools have been applied to conduct proteome-wide association studies (PWASs) by integrating proteomics data with genome-wide association study (GWAS) summary data. The genetic effects of PWAS-identified significant genes are potentially mediated through genetically regulated protein abundance, thus informing the underlying disease mechanisms better than GWAS loci. However, existing TWAS/PWAS tools are limited by considering only one statistical model.

Proteome-wide association studies using summary pQTL data of three tissues identified 30 risk genes of Alzheimer's disease dementia.

Background: Proteome-wide association study (PWAS) integrating proteomic data with genome-wide association study (GWAS) summary data is a powerful tool for studying Alzheimer's disease (AD) dementia. Existing PWAS analyses of AD often rely on the availability of individual-level proteomic and genetic data of a reference panel. Leveraging summary protein quantitative trait loci (pQTL) reference data of multiple AD-relevant tissues is expected to improve PWAS findings of AD dementia.

SR-TWAS: Leveraging Multiple Reference Panels to Improve TWAS Power by Ensemble Machine Learning.

Multiple reference panels of a given tissue or multiple tissues often exist, and multiple regression methods could be used for training gene expression imputation models for TWAS. To leverage expression imputation models (i.e.

TIGAR-V2: Efficient TWAS tool with nonparametric Bayesian eQTL weights of 49 tissue types from GTEx V8.

Standard transcriptome-wide association study (TWAS) methods first train gene expression prediction models using reference transcriptomic data and then test the association between the predicted genetically regulated gene expression and phenotype of interest. Most existing TWAS tools require cumbersome preparation of genotype input files and extra coding to enable parallel computation. To improve the efficiency of TWAS tools, we developed Transcriptome-Integrated Genetic Association Resource V2 (TIGAR-V2), which directly reads Variant Call Format (VCF) files, enables parallel computation, and reduces up to 90% of computation cost (mainly due to loading genotype data) compared to the original version.