Osteoporosis International

, Volume 23, Issue 2, pp 781–787

Genetic variants in the SOX6 gene are associated with bone mineral density in both Caucasian and Chinese populations

Original Article

Abstract

Summary

Given the biological function of SOX6 and recent genome-wide association finding, we performed a fine-mapping association analyses to investigate the relationship between SOX6 and BMD both in Caucasian and Chinese populations. We identified many single-nucleotide polymorphisms (SNPs) within or near the SOX6 gene to be significantly associated with hip bone mineral density (BMD).

Introduction

SOX6 gene is an essential transcription factor in chondrogenesis and cartilage formation. Recent genome-wide association studies (GWAS) detected a SNP (rs7117858) located at the downstream of SOX6 significantly associated with hip BMD.

Methods

Given the biological function of SOX6 and the GWAS finding, we considered SOX6 as a new candidate for BMD and osteoporosis. Therefore, in this study, we performed a fine-mapping association analyses to investigate the relationship between SNPs within and near the SOX6 gene and BMD at both hip and spine. A total of 301 SNPs were tested in two independent US Caucasian populations (2,286 and 1,000 unrelated subjects, respectively) and a Chinese population (1,627 unrelated Han subjects).

Results

We confirmed that the previously reported rs7117858-A was associated with reduced hip BMD, with combined P value of 2.45 × 10−4. Besides this SNP, we identified another 19 SNPs within or near the SOX6 gene to be significantly associated with hip BMD after false discovery rate adjustment. The most significant SNP was rs1347677 located at the intron 3 (P = 3.15 × 10−7). Seven additional SNPs in high linkage disequilibrium with rs1347677 were also significantly associated with hip BMD. SNPs in SOX6 showed significant skeletal site specificity since no SNP was detected to be associated with spine BMD.

Conclusion

Our study identified many SNPs in the SOX6 gene associated with hip BMD even across different ethnicities, which further highlighted the importance of the SOX6 gene influencing BMD variation and provided more information to the understanding of the genetic architecture of osteoporosis.

Keywords

Association BMD Osteoporosis SOX6 

Supplementary material

198_2011_1626_MOESM1_ESM.doc (274 kb)
Supplementary Table 1Properties of SNPs tested in this study (DOC 274 kb)

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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2011

Authors and Affiliations

  1. 1.Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and TechnologyXi’an Jiaotong UniversityXi’anPeople’s Republic of China
  2. 2.Institute of Bioscience and Biotechnology, School of ScienceBeijing Jiaotong UniversityBeijingPeople’s Republic of China
  3. 3.School of Public Health and Tropical MedicineTulane UniversityNew OrleansUSA

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