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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 ≈ 0). 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 (OR interaction 0. 991, 95% CI 0. 987–0. 995, p interaction = 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.
Song et al. (Thu,) studied this question.
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