Osteoporosis International

, Volume 19, Issue 3, pp 303–310

A whole genome linkage scan for QTLs underlying peak bone mineral density

Authors

  • F. Zhang
    • The Key Laboratory of Biomedical Information Engineering of the Ministry of Education and Institute of Molecular Genetics, School of Life Science and TechnologyXi’an Jiaotong University
    • Department of Biomedical Sciences and Osteoporosis Research Center, School of MedicineCreighton University
  • P. Xiao
    • Department of Biomedical Sciences and Osteoporosis Research Center, School of MedicineCreighton University
  • F. Yang
    • Department of Biomedical Sciences and Osteoporosis Research Center, School of MedicineCreighton University
    • Laboratory of Molecular and Statistical Genetics, College of Life SciencesHunan Normal University
  • H. Shen
    • Department of Biomedical Sciences and Osteoporosis Research Center, School of MedicineCreighton University
  • D.-H. Xiong
    • Department of Biomedical Sciences and Osteoporosis Research Center, School of MedicineCreighton University
  • H.-Y. Deng
    • Department of Orthopaedic Surgery and Basic Medical Sciences, School of MedicineUniversity of Missouri-Kansas City
  • C. J. Papasian
    • Department of Orthopaedic Surgery and Basic Medical Sciences, School of MedicineUniversity of Missouri-Kansas City
  • B. M. Drees
    • Department of Internal Medicine and Basic Medical Sciences, School of MedicineUniversity of Missouri-Kansas City
  • J. J. Hamilton
    • Department of Orthopaedic Surgery and Basic Medical Sciences, School of MedicineUniversity of Missouri-Kansas City
  • R. R. Recker
    • Department of Biomedical Sciences and Osteoporosis Research Center, School of MedicineCreighton University
    • The Key Laboratory of Biomedical Information Engineering of the Ministry of Education and Institute of Molecular Genetics, School of Life Science and TechnologyXi’an Jiaotong University
    • Department of Biomedical Sciences and Osteoporosis Research Center, School of MedicineCreighton University
    • Department of Orthopaedic Surgery and Basic Medical Sciences, School of MedicineUniversity of Missouri-Kansas City
Original Article

DOI: 10.1007/s00198-007-0468-z

Cite this article as:
Zhang, F., Xiao, P., Yang, F. et al. Osteoporos Int (2008) 19: 303. doi:10.1007/s00198-007-0468-z

Abstract

Summary

We conducted a whole genome linkage scan for quantitative trait loci (QTLs) underlying peak bone mineral density (PBMD). Our efforts identified several potential genomic regions for PBMD and highlighted the importance of epistatic interaction and sex-specific analyses in identifying genetic regions underlying PBMD variation.

Introduction

Peak bone mineral density (PBMD) is an important clinical risk predictor of osteoporosis and explains a large part of bone mineral density (BMD) variation.

Methods

To detect susceptive quantitative trait loci (QTLs) for PBMD variation including consideration of epistatic and sex-specific effects, we conducted a whole genome linkage scan (WGLS) for PBMD using 2,200 Caucasians from 207 pedigrees, aged 20–50 years. All the individuals were genotyped with 410 microsatellite markers. In addition to WGLS in the total combined sample of males and females, we conducted epistatic interaction analyses, and sex-specific subgroup linkage analyses.

Results

We identified several potential genomic regions that met the criteria for suggestive linkage. The most impressing region is 12p12 for hip PBMD (LOD = 2.79) in the total sample. Epistatic interaction analyses found a significant epistatic interaction between 12p12 and 22q13 (p = 0.0021) for hip PBMD. Additionally, we detected suggestive linkage evidence at 15q26 (LOD = 2.93), 2p13 (LOD = 2.64), and Xq27 (LOD = 2.64). Sex-specific analyses suggested the presence of sex-specific QTLs for PBMD variation.

Conclusions

Our efforts identified several potential regions for PBMD and highlighted the importance of epistatic interaction and sex-specific analyses in identifying genetic regions underlying PBMD variation.

Keywords

Epistatic interactionPBMDQTLSex-specificWhole genome linkage scan

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2007