ASTWAS: modeling alternative polyadenylation and SNP effects in kernel-driven TWAS reveal novel genetic associations for complex traits.

ABSTRACT: Alternative polyadenylation (APA) of $3^{\prime}$untranslated regions ($3^{\prime}$UTRs) is a pervasive mechanism that regulates mRNA stability, localization, and translational efficiency by generating isoforms with distinct $3^{\prime}$UTR lengths and regulatory element composition. Despite its critical role in fine-tuning gene expression, APA has been largely overlooked in transcriptome-wide association studies (TWAS), which traditionally rely on linear models of SNP effects. To bridge this gap, we developed ASTWAS, a two-stage framework that first trains APA usage prediction models (BLUP, Elastic Net, LASSO, and TOP1) to quantify SNP impacts on distal poly(A) site choice via the percentage of distal poly(A) site usage index, and then aggregates weighted SNP effects within a kernel metho

SUBMITTER: Wang Y 

PROVIDER: S-EPMC12814985 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature