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Osteoporos Int. 2019 Dec 1. doi: 10.1007/s00198-019-05244-8. [Epub ahead of print]

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

Xiao X1,2, Wu Q3,4.

Author information

1
Nevada Institute of Personalized Medicine, University of Nevada, Las Vegas, NV, USA.
2
Department of Environmental and Occupational Health, School of Public Health, University of Nevada, Las Vegas, NV, USA.
3
Nevada Institute of Personalized Medicine, University of Nevada, Las Vegas, NV, USA. qing.wu@unlv.edu.
4
Department of Environmental and Occupational Health, School of Public Health, University of Nevada, Las Vegas, NV, USA. qing.wu@unlv.edu.

Abstract

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.

KEYWORDS:

African American women; Bone mineral density; Genetic risk score; Osteoporosis

PMID:
31786628
DOI:
10.1007/s00198-019-05244-8

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