Bayesian genome-wide TWAS with reference transcriptomic data of brain and blood tissues identified 93 risk genes for Alzheimer's disease dementia.

Background: Transcriptome-wide association study (TWAS) is an influential tool for identifying novel genes associated with complex diseases, where their genetic effects may be mediated through transcriptome. TWAS utilizes reference genetic and transcriptomic data to estimate genetic effect sizes on expression quantitative traits of target genes (i.e., effect sizes of a broad sense of expression quantitative trait loci, eQTL). These estimated effect sizes are then employed as variant weights in burden gene-based association test statistics, facilitating the mapping of risk genes for complex diseases with genome-wide association study (GWAS) data. However, most existing TWAS of Alzheimer's disease (AD) dementia have primarily focused on Methods: We first applied BGW-TWAS to the Genotype-Tissue Expression (GTEx) V8 dataset to estimate Results: We identified 37 genes in prefrontal cortex, 55 in cortex, and 51 in whole blood that were significantly associated with AD dementia. By combining BGW-TWAS p-values across these three tissues, we obtained 93 significant risk genes including 29 genes primarily due to Conclusion: We applied BGW-TWAS and aggregated Cauchy test methods to integrate both