Genome-wide association study for femoral neck bone geometry

Authors

  • Lan-Juan Zhao,

    1. Osteoporosis Research Center, Creighton University Medical Center, Omaha, NE, USA
    2. School of Medicine, University of Missouri–Kansas City, Kansas City, MO, USA
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  • Xiao-Gang Liu,

    1. Key Laboratory of Biomedical Information Engineering, Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shanxi 710049, Peoples Republic of China
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  • Yao-Zhong Liu,

    1. School of Medicine, University of Missouri–Kansas City, Kansas City, MO, USA
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  • Yong-Jun Liu,

    1. School of Medicine, University of Missouri–Kansas City, Kansas City, MO, USA
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  • Christopher J Papasian,

    1. School of Medicine, University of Missouri–Kansas City, Kansas City, MO, USA
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  • Bao-Yong Sha,

    1. Osteoporosis Research Center, Creighton University Medical Center, Omaha, NE, USA
    2. Laboratory of Molecular and Statistical Genetics, College of Life Sciences Hunan Normal University, Changsha, Hunan 410081, Peoples Republic of China
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  • Feng Pan,

    1. Key Laboratory of Biomedical Information Engineering, Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shanxi 710049, Peoples Republic of China
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  • Yan-Fang Guo,

    1. Key Laboratory of Biomedical Information Engineering, Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shanxi 710049, Peoples Republic of China
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  • Liang Wang,

    1. Key Laboratory of Biomedical Information Engineering, Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shanxi 710049, Peoples Republic of China
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  • Han Yan,

    1. Key Laboratory of Biomedical Information Engineering, Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shanxi 710049, Peoples Republic of China
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  • Dong-Hai Xiong,

    1. School of Medicine, University of Missouri–Kansas City, Kansas City, MO, USA
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  • Zi-Hui Tang,

    1. Laboratory of Molecular and Statistical Genetics, College of Life Sciences Hunan Normal University, Changsha, Hunan 410081, Peoples Republic of China
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  • Tie-Lin Yang,

    1. Key Laboratory of Biomedical Information Engineering, Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shanxi 710049, Peoples Republic of China
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  • Xiang-Ding Chen,

    1. Laboratory of Molecular and Statistical Genetics, College of Life Sciences Hunan Normal University, Changsha, Hunan 410081, Peoples Republic of China
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  • Yan Guo,

    1. Key Laboratory of Biomedical Information Engineering, Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shanxi 710049, Peoples Republic of China
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  • Jian Li,

    1. School of Medicine, University of Missouri–Kansas City, Kansas City, MO, USA
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  • Hui Shen,

    1. School of Medicine, University of Missouri–Kansas City, Kansas City, MO, USA
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  • Feng Zhang,

    1. Key Laboratory of Biomedical Information Engineering, Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shanxi 710049, Peoples Republic of China
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  • Shu-Feng Lei,

    1. Laboratory of Molecular and Statistical Genetics, College of Life Sciences Hunan Normal University, Changsha, Hunan 410081, Peoples Republic of China
    2. School of Medicine, University of Missouri–Kansas City, Kansas City, MO, USA
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  • Robert R Recker,

    1. Osteoporosis Research Center, Creighton University Medical Center, Omaha, NE, USA
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  • Hong-Wen Deng

    Corresponding author
    1. Laboratory of Molecular and Statistical Genetics, College of Life Sciences Hunan Normal University, Changsha, Hunan 410081, Peoples Republic of China
    2. Key Laboratory of Biomedical Information Engineering, Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shanxi 710049, Peoples Republic of China
    3. School of Medicine, University of Missouri–Kansas City, Kansas City, MO, USA
    • Departments of Basic Medical Science and Orthopedic Surgery, University of Missouri–Kansas City, 2411 Holmes Street, Room M3-C03, Kansas City, MO 64108, USA.
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Abstract

Poor femoral neck bone geometry at the femur is an important risk factor for hip fracture. We conducted a genome-wide association study (GWAS) of femoral neck bone geometry, examining approximately 379,000 eligible single-nucleotide polymorphisms (SNPs) in 1000 Caucasians. A common genetic variant, rs7430431 in the receptor transporting protein 3 (RTP3) gene, was identified in strong association with the buckling ratio (BR, P = 1.6 × 10−7), an index of bone structural instability, and with femoral cortical thickness (CT, P = 1.9 × 10−6). The RTP3 gene is located in 3p21.31, a region that we found to be linked with CT (LOD = 2.19, P = 6.0 × 10−4) in 3998 individuals from 434 pedigrees. The replication analyses in 1488 independent Caucasians and 2118 Chinese confirmed the association of rs7430431 to BR and CT (combined P = 7.0 × 10−3 for BR and P = 1.4 × 10−2 for CT). In addition, 350 hip fracture patients and 350 healthy control individuals were genotyped to assess the association of the RTP3 gene with the risk of hip fracture. Significant association between a nearby common SNP, rs10514713 of the RTP3 gene, and hip fracture (P = 1.0 × 10−3) was found. Our observations suggest that RTP3 may be a novel candidate gene for femoral neck bone geometry. © 2010 American Society for Bone and Mineral Research

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