Mapping Quantitative Trait Loci for Cross-Sectional Geometry at the Femoral Neck

Authors

  • Hui Shen,

    1. Osteoporosis Research Center, Creighton University, Omaha, Nebraska, USA
    2. Department of Biomedical Sciences, Creighton University, Omaha, Nebraska, USA
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  • Ji-Rong Long,

    1. Osteoporosis Research Center, Creighton University, Omaha, Nebraska, USA
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  • Dong-Hai Xiong,

    1. Osteoporosis Research Center, Creighton University, Omaha, Nebraska, USA
    2. Department of Biomedical Sciences, Creighton University, Omaha, Nebraska, USA
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  • Yong-Jun Liu,

    1. Osteoporosis Research Center, Creighton University, Omaha, Nebraska, USA
    2. Department of Biomedical Sciences, Creighton University, Omaha, Nebraska, USA
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  • Yao-Zhong Liu,

    1. Osteoporosis Research Center, Creighton University, Omaha, Nebraska, USA
    2. Department of Biomedical Sciences, Creighton University, Omaha, Nebraska, USA
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  • Peng Xiao,

    1. Osteoporosis Research Center, Creighton University, Omaha, Nebraska, USA
    2. Department of Biomedical Sciences, Creighton University, Omaha, Nebraska, USA
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  • Lan-Juan Zhao,

    1. Osteoporosis Research Center, Creighton University, Omaha, Nebraska, USA
    2. Department of Biomedical Sciences, Creighton University, Omaha, Nebraska, USA
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  • Volodymyr Dvornyk,

    1. Osteoporosis Research Center, Creighton University, Omaha, Nebraska, USA
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  • Yuan-Yuan Zhang,

    1. Osteoporosis Research Center, Creighton University, Omaha, Nebraska, USA
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  • Sonia Rocha-Sanchez,

    1. Department of Biomedical Sciences, Creighton University, Omaha, Nebraska, USA
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  • Peng-Yuan Liu,

    1. Osteoporosis Research Center, Creighton University, Omaha, Nebraska, USA
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  • Jin-Long Li,

    1. Seattle Biomedical Research Institute, Seattle, Washington, USA
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  • Hong-Wen Deng PhD

    Corresponding author
    1. Osteoporosis Research Center, Creighton University, Omaha, Nebraska, USA
    2. Department of Biomedical Sciences, Creighton University, Omaha, Nebraska, USA
    3. The Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
    4. Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, ChangSha, Hunan, China
    • Osteoporosis Research Center, Creighton University, North 30th Street, Suite 6787, Omaha, NE 68131, USA
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  • The authors have no conflict of interest.

Abstract

A genome-wide linkage scan was performed in a sample of 79 multiplex pedigrees to identify genomic regions linked to femoral neck cross-sectional geometry. Potential quantitative trait loci were detected at several genomic regions, such as 10q26, 20p12-q12, and chromosome X.

Introduction: Bone geometry is an important determinant of bone strength and osteoporotic fractures. Previous studies have shown that femoral neck cross-sectional geometric variables are under genetic controls. To identify genetic loci underlying variation in femoral neck cross-sectional geometry, we conducted a whole genome linkage scan for four femoral neck cross-sectional geometric variables in 79 multiplex white pedigrees.

Materials and Methods: A total of 1816 subjects from 79 pedigrees were genotyped with 451 microsatellite markers across the human genome. We performed linkage analyses on the entire data, as well as on men and women separately.

Results: Significant linkage evidence was identified at 10q26 for buckling ratio (LOD = 3.27) and Xp11 (LOD = 3.45) for cortical thickness. Chromosome region 20p12-q12 showed suggestive linkage with cross-sectional area (LOD = 2.33), cortical thickness (LOD = 2.09), and buckling ratio (LOD = 1.94). Sex-specific linkage analyses further supported the importance of 20p12-q12 for cortical thickness (LOD = 2.74 in females and LOD = 1.88 in males) and buckling ratio (LOD = 5.00 in females and LOD = 3.18 in males).

Conclusions: This study is the first genome-wide linkage scan searching for quantitative trait loci underlying femoral neck cross-sectional geometry in humans. The identification of the genes responsible for bone geometric variation will improve our knowledge of bone strength and aid in development of diagnostic approaches and interventions for osteoporotic fractures.

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