Osteoporosis International

, Volume 21, Issue 5, pp 785–795

Replication study of candidate genes/loci associated with osteoporosis based on genome-wide screening

  • Y.-P. Zhang
  • F.-Y. Deng
  • Y. Chen
  • Y.-F. Pei
  • Y. Fang
  • Y.-F. Guo
  • X. Guo
  • X.-G. Liu
  • Q. Zhou
  • Y.-J. Liu
  • H.-W. Deng
Original Article

DOI: 10.1007/s00198-009-1014-y

Cite this article as:
Zhang, YP., Deng, FY., Chen, Y. et al. Osteoporos Int (2010) 21: 785. doi:10.1007/s00198-009-1014-y

Abstract

Summary

Osteoporosis is a major public health problem characterized by low bone mineral density (BMD). This replication study confirmed 38 single-nucleotide polymorphisms (SNPs) out of 139 SNPs previously reported in three recent genome-wide association studies (GWASs) in an independent US white sample. Ten SNPs achieved combined p < 3.6 × 10−4.

Introduction

BMD is under strong genetic control. This study aims to verify the potential associations between BMD and candidate genes/loci reported by GWAS of FHS100K, Icelandic deCODE, and UK-NL.

Methods

Eight promising (at the genome-wide significant level after Bonferroni correction) and 131 available sub-promising (at the most stringent p value, p < 5.5 × 10−5 in the three GWASs reports) SNPs were selected. By using genotypic information from Affymetrix 500 K SNP arrays, we tested their associations with BMD in 1,000 unrelated US whites. Fisher's combined probability method was used to quantify the overall evidence of association. BMD was measured by dual energy X-ray absorptiometry.

Results

Two promising SNPs, rs3762397 and rs3736228, were replicated in the current study with p < 0.05. Besides, 36 sub-promising SNPs were replicated at the same significant level. Ten SNPs achieved significant combined p < 3.6 × 10−4 (0.05/139 SNPs, corrected for multiple testing).

Conclusions

Osteoporosis susceptibility of 38 SNPs was replicated in 1,000 unrelated US whites. This study showed promise for replication of some initial genome-wide association signals.

Keywords

Bone mineral density Genome-wide association Osteoporosis Replication 

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2009

Authors and Affiliations

  • Y.-P. Zhang
    • 1
  • F.-Y. Deng
    • 2
  • Y. Chen
    • 3
  • Y.-F. Pei
    • 3
  • Y. Fang
    • 2
  • Y.-F. Guo
    • 2
    • 3
  • X. Guo
    • 1
  • X.-G. Liu
    • 3
  • Q. Zhou
    • 3
  • Y.-J. Liu
    • 2
  • H.-W. Deng
    • 2
    • 3
    • 4
  1. 1.Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, College of MedicineXi’an Jiaotong UniversityXi’anPeople’s Republic of China
  2. 2.Departments of Orthopedic Surgery and Basic Medical SciencesUniversity of MissouriKansas CityUSA
  3. 3.Key Laboratory of Biomedical Information Engineering, Ministry of Education and Institute of Molecular Genetics, School of Life Science and TechnologyXi’an Jiaotong UniversityXi’anPeople’s Republic of China
  4. 4.College of Life Sciences and EngineeringBeijing Jiao Tong UniversityBeijingPeople’s Republic of China

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