Department of Statistics & Research Institute of Natural Sciences, Sookmyung Women's University, Seoul, 04310, Korea.
Department of Internal Medicine, Seoul National University Hospital, Seoul, 03080, Korea.
Sci Rep. 2024 Mar 21;14(1):6790. doi: 10.1038/s41598-024-55945-2.
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 ). 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 0.991, 95% CI 0.987-0.995, p = 4.93 × 10) 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.
遗传和环境风险因素的联合建模可以提供重要信息，以预测 2 型糖尿病（T2D）的风险。因此，为了预测 T2D 的遗传风险，我们使用一个韩国队列 KARE（745 例病例和 2549 例对照）的基因型数据和日本生物银行的全基因组关联研究汇总统计数据构建了多基因风险评分（PRS）。我们在一个独立的韩国队列 HEXA（5684 例病例和 35703 例对照）中评估了 PRS 的性能。T2D 患者的 PRS 平均值明显高于对照组（0.492 对-0.078，p<0.001）。PRS 预测 T2D 的风险，AUC 为 0.658（95%CI 0.651-0.666）。我们还在 HEXA 队列中评估了 PRS 与腰围（WC）之间的交互作用。PRS 与 WC 呈显著亚乘法交互作用（OR 0.991，95%CI 0.987-0.995，p=4.93×10）。随着 PRS 的增加，WC 对 T2D 的影响呈下降趋势。性别特异性分析产生了类似的交互作用结果，表明随着 PRS 的增加，WC 对 T2D 的影响降低。总之，WC 对 T2D 的风险可能因 PRS 而异，那些具有高 PRS 的人可能会以较低的 WC 阈值患上 T2D。我们的研究结果有望提高 T2D 的风险预测能力，并有助于识别 T2D 风险增加的个体。
