Association between a literature-based genetic risk score and bone mineral density of African American women in Women Health Initiative Study

  • X. Xiao
  • Q. WuEmail author
Original Article



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.


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.


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.


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.


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.


Genetic risk score Bone mineral density Osteoporosis African American women 



Genetic risk score


Bone mineral density


Single-nucleotide polymorphism


Genome-wide association study


The database of Genotypes and Phenotypes


Women’s Health Initiative


Women’s Health Initiative – SNP Health Association Resource


Funding information

The research and analysis described in the current publication was supported by a grant from the National Institute of General Medical Sciences (GR08954), the Genome Acquisition to Analytics (GAA) Research Core of the Personalized Medicine Center of Biomedical Research Excellence in the Nevada Institute of Personalized Medicine, and the National Supercomputing Institute at the University of Nevada Las Vegas.

Compliance with ethical standards

Conflicts of interest



The funding sponsor was not involved in the analysis design, genotype imputation, data analysis, and interpretation of the analysis results or the preparation, review, and approval of this manuscript.

Supplementary material

198_2019_5244_MOESM1_ESM.docx (458 kb)
ESM 1 (DOCX 457 kb)


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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2019

Authors and Affiliations

  1. 1.Nevada Institute of Personalized MedicineUniversity of NevadaLas VegasUSA
  2. 2.Department of Environmental and Occupational Health, School of Public HealthUniversity of NevadaLas VegasUSA

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