Department of Epidemiology, School of Public Health, and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases Medical College of Soochow University, Suzhou, China (M.S.).
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (M.S., W.C., X.S., L.A.B., J.H., A.C.R., C.L., L.Q., T.N.K.).
Circ Genom Precis Med. 2022 Aug;15(4):e003375. doi: 10.1161/CIRCGEN.121.003375. Epub 2022 Jun 8.
Genetic information may help to identify individuals in childhood who are at increased risk for cardiometabolic disease.
We included 1201 BHS (Bogalusa Heart Study) participants (832 White participants and 369 Black participants) who were followed up to 42.3 years, starting at a mean age of 9.8 years. A validated genome-wide polygenic risk score (PRS) was tested for association with midlife body mass index (BMI), fasting plasma glucose, and systolic blood pressure using multiple linear regression models. Cox proportional hazards models tested associations of the PRS with incident obesity, diabetes, and hypertension. All analyses were conducted according to race and adjusted for baseline age, sex, ancestry, and BMI.
The constructed PRS was significantly and modestly correlated with midlife BMI in both White and Black participants, with correlation coefficients of 0.27 (=1.94×10) and 0.16 (=5.50×10), respectively. In White participants, per SD increase of PRS was associated with an average 1.29 kg/m higher BMI (=4.44×10), 2.82 mg/dL higher fasting plasma glucose (=1.17×10), and 1.09 mm Hg higher systolic blood pressure (=3.57×10) at midlife. The PRS also conferred a 26% higher increased risk of obesity (=3.50×10) in White participants. In addition, the variance in midlife BMI explained increased from 0.1973 to 0.2293 when PRS was added to the model including age, sex, principal components, and baseline BMI (<0.0001). No associations were observed in Black participants.
Adiposity-related genetic information independently predicted cardiometabolic health in White BHS participants. Null associations observed in Black BHS participants highlight the urgent need for PRS development in multi-ancestry populations.
遗传信息可能有助于识别儿童时期患心血管代谢疾病风险增加的个体。
我们纳入了 1201 名 BHS（博加卢萨心脏研究）参与者（832 名白种人参与者和 369 名黑人参与者），这些参与者的随访时间长达 42.3 年，起始年龄平均为 9.8 岁。使用多线性回归模型，对经过验证的全基因组多基因风险评分（PRS）与中年时期的体重指数（BMI）、空腹血糖和收缩压之间的关联进行了测试。Cox 比例风险模型测试了 PRS 与肥胖、糖尿病和高血压发病的关联。所有分析均根据种族进行，并根据基线年龄、性别、祖源和 BMI 进行了调整。
构建的 PRS 与白人和黑人参与者的中年 BMI 显著且适度相关，相关系数分别为 0.27（=1.94×10）和 0.16（=5.50×10）。在白人参与者中，PRS 每增加一个标准差，与中年时期 BMI 平均增加 1.29kg/m（=4.44×10）、空腹血糖增加 2.82mg/dL（=1.17×10）和收缩压增加 1.09mmHg（=3.57×10）相关。PRS 还使白人参与者肥胖的风险增加了 26%（=3.50×10）。此外，当将 PRS 添加到包括年龄、性别、主成分和基线 BMI 的模型中时，中年 BMI 的方差解释度从 0.1973 增加到 0.2293（<0.0001）。在黑人参与者中未观察到相关性。
与肥胖相关的遗传信息独立预测了 BHS 白人参与者的心血管代谢健康。在 BHS 黑人参与者中观察到的无效关联突显了在多祖源人群中开发 PRS 的迫切需要。
