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ارتباط بین نمره خطر ژنتیکی مبتنی بر موارد چاپی و تراکم معدنی استخوان زنان آمریکایی آفریقایی تبار در مطالعه ابتکار بهداشت زنان

Association between a literature-based genetic risk score and bone mineral density of African American women in Women Health Initiative Study
نویسنده: X. Xiao, Q. Wu
سال انتشار: a2020
زبان فایل: انگلیسی
فرمت فایل: pdf
قیمت: 100,000ريال

افزودن به سبد دانلود

DOI: 10.1007/s00198-019-05244-8

Abstract

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.