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

Xiao, X.; Wu, Q.

Affiliations

¹Nevada Institute of Personalized Medicine, University of Nevada, Las Vegas, USA

²Department of Environmental and Occupational Health, School of Public Health, University of Nevada, Las Vegas, USA

Abstract and keywords

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

Links

DOI: 10.1007/s00198-019-05244-8

PubMed: 31786628

WoS: 000499558000001

History

Received: 2019-08-26

Accepted: 2019-11-19

Online: 2019-12-01

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Cited By (1)

Year	Entry
2021	Yau MS, Kuipers AL, Price R, Nicolas A, Tajuddin SM, Handelman SK, Arbeeva L, Chesi A, Hsu Y, Liu C, Karasik D, Zemel BS, Grant SF, Jordan JM, Jackson RD, Evans MK, Harris TB, Zmuda JM, Kiel DP. A meta‐analysis of the transferability of bone mineral density genetic loci associations from European to African ancestry populations. J Bone Miner Res. March 2021;36(3):469-479.