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

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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.

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Acknowledgements

Investigators of this work were partially supported by grants from NIH (K01 AR021170-01, R01 AR45349-01, and R01 GM60402-01A1) and an LB595 grant from the State of Nebraska. The study was also benefitted from grants from National Science Foundation of China, Huo Ying Dong Education Foundation, Hunan Province, Xi’an Jiaotong University, and the Ministry of Education of China. The genotyping experiment was performed by Marshfield Center for Medical Genetics and supported by NHLBI Mammalian Genotyping Service (Contract Number HV48141).

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Authors and Affiliations

  1. The 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 University, Xi’an, 710049, People’s Republic of China

    F. Zhang & H.-W. Deng

  2. Department of Biomedical Sciences and Osteoporosis Research Center, School of Medicine, Creighton University, Omaha, NE, 68131, USA

    F. Zhang, P. Xiao, F. Yang, H. Shen, D.-H. Xiong, R. R. Recker & H.-W. Deng

  3. Department of Orthopaedic Surgery and Basic Medical Sciences, School of Medicine, University of Missouri-Kansas City, 2411 Holmes Street, Room M3-C03, Kansas City, MO, 64108, USA

    H.-Y. Deng, C. J. Papasian, J. J. Hamilton & H.-W. Deng

  4. Department of Internal Medicine and Basic Medical Sciences, School of Medicine, University of Missouri-Kansas City, Kansas City, MO, 64108, USA

    B. M. Drees

  5. Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan, 410081, People’s Republic of China

    F. Yang

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  1. F. Zhang
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  2. P. Xiao
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Corresponding author

Correspondence to H.-W. Deng.

Additional information

Feng Zhang and Peng Xiao contributed equally to this article

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Zhang, F., Xiao, P., Yang, F. et al. A whole genome linkage scan for QTLs underlying peak bone mineral density. Osteoporos Int 19, 303–310 (2008). https://doi.org/10.1007/s00198-007-0468-z

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  • DOI: https://doi.org/10.1007/s00198-007-0468-z

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