Original Article

Osteoporosis International

, Volume 19, Issue 3, pp 303-310

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

  • F. ZhangAffiliated withThe Key Laboratory of Biomedical Information Engineering of the Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi’an Jiaotong UniversityDepartment of Biomedical Sciences and Osteoporosis Research Center, School of Medicine, Creighton University
  • , P. XiaoAffiliated withDepartment of Biomedical Sciences and Osteoporosis Research Center, School of Medicine, Creighton University
  • , F. YangAffiliated withDepartment of Biomedical Sciences and Osteoporosis Research Center, School of Medicine, Creighton UniversityLaboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University
  • , H. ShenAffiliated withDepartment of Biomedical Sciences and Osteoporosis Research Center, School of Medicine, Creighton University
  • , D.-H. XiongAffiliated withDepartment of Biomedical Sciences and Osteoporosis Research Center, School of Medicine, Creighton University
  • , H.-Y. DengAffiliated withDepartment of Orthopaedic Surgery and Basic Medical Sciences, School of Medicine, University of Missouri-Kansas City
  • , C. J. PapasianAffiliated withDepartment of Orthopaedic Surgery and Basic Medical Sciences, School of Medicine, University of Missouri-Kansas City
  • , B. M. DreesAffiliated withDepartment of Internal Medicine and Basic Medical Sciences, School of Medicine, University of Missouri-Kansas City
  • , J. J. HamiltonAffiliated withDepartment of Orthopaedic Surgery and Basic Medical Sciences, School of Medicine, University of Missouri-Kansas City
    • , R. R. ReckerAffiliated withDepartment of Biomedical Sciences and Osteoporosis Research Center, School of Medicine, Creighton University
    • , H.-W. DengAffiliated withThe Key Laboratory of Biomedical Information Engineering of the Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi’an Jiaotong UniversityDepartment of Biomedical Sciences and Osteoporosis Research Center, School of Medicine, Creighton UniversityDepartment of Orthopaedic Surgery and Basic Medical Sciences, School of Medicine, University of Missouri-Kansas City Email author 

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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 interaction PBMD QTL Sex-specific Whole genome linkage scan