Nevada Institute of Personalized Medicine, College of Science, University of Nevada, Las Vegas, NV, USA.
Department of Epidemiology and Biostatistics, School of Public Health, University of Nevada Las Vegas, Las Vegas, NV, USA.
Osteoporos Int. 2023 May;34(5):943-953. doi: 10.1007/s00198-023-06712-y. Epub 2023 Feb 25.
Whether the PGS developed using data from European ancestry is predictive of fracture risk for minorities remains unclear. This study demonstrated that PGSs based on common BMD-related genetic variants discovered in the European ancestry cohort are predictive of fracture risk in people of Asian but not African ancestry.
Large-scale genome-wide association studies (GWAS) on bone mineral density (BMD) have been conducted predominantly in European cohorts. Genetic models based on common variants associated with BMD have been evaluated using almost exclusively European data, which could potentially exacerbate health disparities due to different linkage disequilibrium among different ethnic groups.
UK Biobank (UKB) is a large-scale population-based observational study starting in 2006 that recruited 502,617 individuals aged between 40 and 69 years with genotypic and phenotypic data available. Based on the summary statistics of two GWAS studies of femoral neck BMD and total body BMD, we derived four PGSs and assessed the association between each PGS and prevalent/incident fractures within each ethnic group separately using Multivariate logistic regressions and Cox proportional hazard models. All models were adjusted for age, sex, and the first four principal components.
We assessed four PGSs derived from European cohorts. Significant associations were observed between PGSs and fracture in European and Asian cohorts but not in the African cohort. Of all four PGSs, [Formula: see text] performed the best. A standard deviation decreases in [Formula: see text] were associated with an increased hazard ratio (HR) of 1.24 (1.22-1.27), 1.28 (0.83-1.99), and 1.34 (1.10-1.64) in European, African, and Asian ancestry, respectively. A low BMD-related PGS is associated with up to 2.35- and 4.31-fold increased fracture risk in European and Asian populations.
These results showed that PGSs based on common BMD-related genetic variants discovered in the European ancestry cohort are predictive of fracture risk in people of Asian but not African ancestry.
使用欧洲血统数据开发的 PGS 是否可预测少数族裔的骨折风险尚不清楚。本研究表明，基于欧洲血统队列中发现的常见与 BMD 相关的遗传变异开发的 PGS 可预测亚洲人群的骨折风险，但不能预测非洲人群的骨折风险。
关于骨密度 (BMD) 的大规模全基因组关联研究 (GWAS) 主要在欧洲队列中进行。基于与 BMD 相关的常见变异的遗传模型已使用几乎完全来自欧洲的数据进行了评估，这可能会由于不同族群之间不同的连锁不平衡而加剧健康差距。
英国生物银行 (UKB) 是一项始于 2006 年的大型基于人群的观察性研究，招募了 502,617 名年龄在 40 至 69 岁之间的个体，具有基因型和表型数据。基于股骨颈 BMD 和全身 BMD 的两项 GWAS 研究的汇总统计数据，我们推导了四个 PGS，并分别使用多元逻辑回归和 Cox 比例风险模型评估了每个 PGS 与每个族群中常见/新发骨折之间的关联。所有模型均调整了年龄、性别和前四个主成分。
我们评估了来自欧洲队列的四个 PGS。在欧洲和亚洲队列中观察到 PGS 与骨折之间存在显著关联，但在非洲队列中未观察到。在所有四个 PGS 中，[Formula: see text]表现最好。[Formula: see text] 每减少一个标准差，欧洲、非洲和亚洲血统的风险比 (HR) 分别增加 1.24(1.22-1.27)、1.28(0.83-1.99)和 1.34(1.10-1.64)。与 BMD 相关的低 PGS 与欧洲和亚洲人群中骨折风险增加高达 2.35 倍和 4.31 倍相关。
这些结果表明，基于欧洲血统队列中发现的常见与 BMD 相关的遗传变异开发的 PGS 可预测亚洲人群的骨折风险，但不能预测非洲人群的骨折风险。
