Genetic risk of low BMD in African American women remains unclear. Based on SNPs discovered from a predominantly Caucasian sample, genetic profile was summarized and was found to be significantly associated with BMD variation in African American women. INTRODUCTION Osteoporosis is largely under-recognized and undertreated in African-American women, the post-fracture morbidity and mortality rates in this racial group is rather high. Since BMD was proved to be highly heritable, based on a comprehensive genome-wide meta-analysis that reported 63 BMD-related single nucleotide polymorphisms (SNPs), we aim to unravel the overall genetic risk for decreased BMD and osteoporosis in African-American women. METHODS Genotype data of 842 African American women in a Women's Health Initiative cohort were analyzed. Comprehensive genotype imputation was conducted at the Sanger Imputation Server. Multi-locus genetic risk scores (GRSs) based on 62 BMD-related single-nucleotide polymorphisms (SNPs) were calculated. The association between GRS and BMD was assessed by regression analysis. Longitudinal data was further analyzed using a generalized estimating equation, which helps achieve more efficient and unbiased regression parameters by accounting for the within-subject correlation of responses on dependent variables. RESULTS After adjusting for age, body weight, hormone use, and previous fracture, for every unit increase of GRS.FN and GRS.LS, BMD at hip and lumbar spine decreased 0.124 g/cm2 and 0.086 g/cm2, respectively. Collectively, the model accounted for 34.95% of the femoral neck BMD variation and 25.79% of lumbar spine BMD variation. Notably, GRS.FN and GRS.LS accounted for 2.03% and 2.39% of the total explained variance, respectively. The proportion of BMD variation can be explained by GRSs increasing as participants aged. CONCLUSIONS Genetic risk score was significantly associated with lower BMD in the current study, suggesting that SNPs discovered from prior meta-analysis based on primarily Caucasian population can also explain a considerable proportion of BMD variation in African Americans.

中文翻译：

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妇女健康倡议研究中基于文献的遗传风险评分与非洲裔美国妇女的骨矿物质密度之间的关联。

非洲裔美国女性低BMD的遗传风险仍不清楚。根据从主要是白种人样本中发现的SNP，总结了遗传特征，发现其与非洲裔美国女性的BMD变异显着相关。简介骨质疏松症在非裔美国女性中普遍被忽视和治疗不足，该种族人群的骨折后发病率和死亡率很高。由于基于全面的全基因组荟萃分析报告了63种与BMD相关的单核苷酸多态性（SNP），因此BMD被证明具有高度的遗传力，因此我们旨在揭示非洲裔美国女性BMD降低和骨质疏松症的总体遗传风险。方法分析了“妇女健康倡议”队列中的842名非洲裔美国妇女的基因型数据。在Sanger插补服务器上进行了全面的基因型插补。计算了基于62个与BMD相关的单核苷酸多态性（SNP）的多基因座遗传风险评分（GRS）。通过回归分析评估了GRS和BMD之间的关联。纵向数据使用广义估计方程进行了进一步分析，该方程通过考虑因变量响应的对象内部相关性，有助于获得更有效和更公正的回归参数。结果在调整了年龄，体重，激素使用量和先前的骨折后，髋关节和腰椎的BMD每增加GRS.FN和GRS.LS，BMD分别降低0.124 g / cm2和0.086 g / cm2。总体而言，该模型占股骨颈BMD变化的34.95％和腰椎BMD变化的25.79％。值得注意的是，GRS。FN和GRS.LS分别占总解释方差的2.03％和2.39％。BMD变化的比例可以用随着参与者年龄的增长而增加的GRS来解释。结论在当前研究中，遗传风险评分与较低的BMD显着相关，这表明从先前基于主要白种人人群的荟萃分析中发现的SNPs也可以解释非裔美国人中BMD变异的相当大的比例。