Original Article

Osteoporosis International

, Volume 23, Issue 7, pp 1867-1875

A follow-up association study of two genetic variants for bone mineral density variation in Caucasians

  • L.-S. ZhangAffiliated withCollege of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University
  • , H.-G. HuAffiliated withCollege of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University
  • , Y.-J. LiuAffiliated withCenter for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, Tulane University School of Public Health and Tropical Medicine
  • , J. LiAffiliated withCenter for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, Tulane University School of Public Health and Tropical Medicine
  • , P. YuAffiliated withCenter for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, Tulane University School of Public Health and Tropical Medicine
  • , F. ZhangAffiliated withThe Key Laboratory of Biomedical Information Engineering, Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi’an Jiaotong University
  • , T.-L. YangAffiliated withThe Key Laboratory of Biomedical Information Engineering, Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi’an Jiaotong University
  • , Q. TianAffiliated withCenter for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, Tulane University School of Public Health and Tropical Medicine
  • , Y.-P. ZhengAffiliated withCollege of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University
    • , Y. GuoAffiliated withThe Key Laboratory of Biomedical Information Engineering, Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi’an Jiaotong University
    • , H.-W. DengAffiliated withCollege of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong UniversityCenter for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, Tulane University School of Public Health and Tropical MedicineCenter of System Biomedical Sciences, Shanghai University of Science and Technology Email author 

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Abstract

Summary

We tested whether two genetic variants were associated with BMD at multiple clinically relevant skeletal sites in Caucasians. We found that variant rs7776725 is consistently associated with hip, spine, wrist and whole-body BMD, which highlights the potential importance of this variant or linked variants for osteoporosis.

Introduction

A recent genome-wide association study identified two single nucleotide polymorphisms (SNPs), rs7776725 and rs1721400, that were associated with bone mineral density (BMD) variation at the radius, tibia and calcaneus in a Korean population. In this study, we aimed to test whether the association of these two genetic variants can be replicated in Caucasians and whether their association with BMD can be extended to other clinically relevant skeletal sites.

Methods

We performed this study in two large cohorts of unrelated US Caucasians. Area BMD at the hip, spine, wrist (ultra-distal radius) and whole body were measured with Hologic dual-energy X-ray absorptiometer. SNPs were genotyped with Affymetrix human genome-wide genotyping arrays. Association analyses were performed using PLINK.

Results

We detected highly significant association (combined p = 1.42 × 10−16) of rs7776725 with wrist BMD but only borderline association signal (combined p = 0.017) for rs1721400 with wrist BMD. In addition, we found that rs7776725 was associated with BMD at the hip, spine and whole body. At the FAM3C gene locus where rs7776725 was located, we identified several other SNPs (rs4727922, rs1803389, rs718766 and rs7793554) that were also associated with BMD.

Conclusions

This is the first follow-up association study of rs7776725 and rs1721400 with BMD. The rs7776725 showed consistent association with BMD at multiple clinically important skeletal sites, which highlighted the potential importance of rs7776725 or linked SNPs for risk of osteoporosis. Further in-depth re-sequencing studies and functional assays are necessary to elucidate the underlying mechanisms.

Keywords

Bone mineral density FAM3C Osteoporosis Single nucleotide polymorphisms