Risk prediction and interaction analysis using polygenic risk score of type 2 diabetes in a Korean population

Abstract

Joint modelling of genetic and environmental risk factors can provide important information to predict the risk of type 2 diabetes (T2D). Therefore, to predict the genetic risk of T2D, we constructed a polygenic risk score (PRS) using genotype data of one Korean cohort, KARE (745 cases and 2549 controls), and the genome-wide association study summary statistics of Biobank Japan. We evaluated the performance of PRS in an independent Korean cohort, HEXA (5684 cases and 35,703 controls). Individuals with T2D had a significantly higher mean PRS than controls (0.492 vs. − 0.078, p≈0\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\approx 0$$\\end{document}). PRS predicted the risk of T2D with an AUC of 0.658 (95% CI 0.651–0.666). We also evaluated interaction between PRS and waist circumference (WC) in the HEXA cohort. PRS exhibited a significant sub-multiplicative interaction with WC (ORinteraction 0.991, 95% CI 0.987–0.995, pinteraction = 4.93 × 10–6) in T2D. The effect of WC on T2D decreased as PRS increased. The sex-specific analyses produced similar interaction results, revealing a decreased WC effect on T2D as the PRS increased. In conclusion, the risk of WC for T2D may differ depending on PRS and those with a high PRS might develop T2D with a lower WC threshold. Our findings are expected to improve risk prediction for T2D and facilitate the identification of individuals at an increased risk of T2D.