Faculty of Sport Sciences, Waseda University, Tokorozawa, Saitama, JAPAN.
Med Sci Sports Exerc. 2024 Oct 1;56(10):2026-2038. doi: 10.1249/MSS.0000000000003477. Epub 2024 May 15.
This study estimated an individual's genetic liability to cardiometabolic risk factors by polygenic risk score (PRS) construction and examined whether high cardiorespiratory fitness (CRF) modifies the association between PRS and cardiometabolic risk factors.
This cross-sectional study enrolled 1296 Japanese adults aged ≥40 yr. The PRS for each cardiometabolic trait (blood lipids, glucose, hypertension, and obesity) was calculated using the LDpred2 and clumping and thresholding methods. Participants were divided into low-, intermediate-, and high-PRS groups according to PRS tertiles for each trait. CRF was quantified as peak oxygen uptake (V̇O 2peak ) per kilogram body weight. Participants were divided into low-, intermediate-, and high-CRF groups according to the tertile V̇O 2peak value.
Linear regression analysis revealed a significant interaction between PRS for triglyceride (PRS TG ) and CRF groups on serum TG levels regardless of the PRS calculation method, and the association between PRS TG and TG levels was attenuated in the high-CRF group. Logistic regression analysis revealed a significant sub-additive interaction between LDpred2 PRS TG and CRF on the prevalence of high TG, indicating that high CRF attenuated the genetic predisposition to high TG. Furthermore, a significant sub-additive interaction between PRS for body mass index and CRF on obesity was detected regardless of the PRS calculation method. These significant interaction effects on high TG and obesity were diminished in the sensitivity analysis using V̇O 2peak per kilogram fat-free mass as the CRF index. Effects of PRSs for other cardiometabolic traits were not significantly attenuated in the high-CRF group regardless of PRS calculation methods.
The findings of the present study suggest that individuals with high CRF overcome the genetic predisposition to high TG levels and obesity.
本研究通过构建多基因风险评分（PRS）来估计个体患心血管代谢危险因素的遗传易感性，并探讨高心肺适能（CRF）是否会改变 PRS 与心血管代谢危险因素之间的关联。
本横断面研究纳入了 1296 名年龄≥40 岁的日本成年人。使用 LDpred2 和聚类与阈值方法计算每个心血管代谢特征（血脂、血糖、高血压和肥胖）的 PRS。根据每个特征的 PRS 三分位数，将参与者分为低、中、高-PRS 组。CRF 被量化为每公斤体重的峰值摄氧量（V̇O2peak）。根据 tertile V̇O2peak 值将参与者分为低、中、高-CRF 组。
线性回归分析显示，无论 PRS 计算方法如何，PRS 甘油三酯（PRS TG）与 CRF 组之间的交互作用与血清 TG 水平显著相关，并且高 CRF 组 PRS TG 与 TG 水平之间的关联减弱。逻辑回归分析显示，LDpred2 PRS TG 与 CRF 对高 TG 患病率的交互作用具有显著的次加性，表明高 CRF 减弱了高 TG 的遗传易感性。此外，无论 PRS 计算方法如何，在 BMI PRS 与 CRF 对肥胖的交互作用中都检测到显著的次加性。在使用每公斤去脂体重的 V̇O2peak 作为 CRF 指数的敏感性分析中，高 TG 和肥胖的这些显著交互作用效应减弱。无论 PRS 计算方法如何，高 CRF 组中其他心血管代谢特征的 PRS 作用均未显著减弱。
本研究结果表明，高 CRF 个体可以克服高 TG 水平和肥胖的遗传易感性。
