TGF-β Pathway-Based Polygenic Risk Score Modifies the Association between Red Meat Intake and Colorectal Cancer Risk: Application of a Novel Pathway-Based PRS Method

Abstract

BACKGROUND: Red meat and/or processed meat are established colorectal cancer risk factors. Genome-wide association studies (GWAS) have reported more than 200 variants associated with colorectal cancer risk. We used functional annotation data to identify subsets of variants within known pathways to construct pathway-based polygenic risk scores (pPRS) to assess interactions with meat intake. METHODS: A pooled sample of 30,812 cases and 40,504 colorectal cancer controls from 27 studies was analyzed. Quantiles for red and processed meat intake were constructed. A total of 204 GWAS variants were annotated to genes with Annotation Query (AnnoQ) and assessed for overrepresentation in PANTHER-report..