Bivariate Whole Genome Linkage Analysis for Femoral Neck Geometric Parameters and Total Body Lean Mass

Authors

  • Fei-Yan Deng,

    1. Laboratory of Molecular and Statistical Genetics and the Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China
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  • Peng Xiao,

    1. Osteoporosis Research Center and Department of Biomedical Sciences, Creighton University Medical Center, Omaha, Nebraska, USA
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  • Shu-Feng Lei,

    1. Laboratory of Molecular and Statistical Genetics and the Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China
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  • Lei Zhang,

    1. Institute of Molecular Genetics and the Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiao Tong University, Xi'an, China
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  • Fang Yang,

    1. Laboratory of Molecular and Statistical Genetics and the Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China
    2. Osteoporosis Research Center and Department of Biomedical Sciences, Creighton University Medical Center, Omaha, Nebraska, USA
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  • Zi-Hui Tang,

    1. Laboratory of Molecular and Statistical Genetics and the Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China
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  • Peng-Yuan Liu,

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

    1. Departments of Orthopedic Surgery and Basic Medical Sciences, University of Missouri-Kansas City, Kansas City, Missouri, USA
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  • Robert R Recker,

    1. Osteoporosis Research Center and Department of Biomedical Sciences, Creighton University Medical Center, Omaha, Nebraska, USA
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  • Hong-Wen Deng PhD

    Corresponding author
    1. Laboratory of Molecular and Statistical Genetics and the Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China
    2. Osteoporosis Research Center and Department of Biomedical Sciences, Creighton University Medical Center, Omaha, Nebraska, USA
    3. Departments of Orthopedic Surgery and Basic Medical Sciences, University of Missouri-Kansas City, Kansas City, Missouri, USA
    • Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China
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  • The authors state that they have no conflicts of interest.

  • Published online on March 12, 2007;

Abstract

A genome-wide bivariate analysis was conducted for femoral neck GPs and TBLM in a large white sample. We found QTLs shared by GPs and TBLM in the total sample and the sex-specific samples. QTLs with potential pleiotropy were also disclosed.

Introduction: Previous studies have suggested that femoral neck cross-section geometric parameters (FNCS-GPs), including periosteal diameter (W), cross-sectional area (CSA), cortical thickness (CT), buckling ratio (BR), and section modulus (Z), are genetically correlated with total body lean mass (TBLM). However, the shared genetic factors between them are unknown.

Materials and Methods: To identify the specific QTLs shared by FNCS-GPs and TBLM, we performed bivariate whole genome linkage analysis (WGLA) in a large sample of 451 white families made up of 4498 subjects.

Results: Multipoint bivariate linkage analyses for 22 autosomes showed evidence of suggestive or significant linkages (thresholds of LOD = 2.3 and 3.7, respectively) to chromosomes 3q12 and 20q13 in the entire sample, 6p25 and 10q24 in women, and 4p15, 5q34–35 and 7q21 in men. Two-point linkage analyses for chromosome X showed strong linkage to Xp22.13, Xp11.4, Xq22.3, Xq23–24, and Xq25. Complete pleiotropy was identified on 10q24 and 5q35 for TBLM and BR in women and for TBLM and CT in men, respectively. Furthermore, chromosomes 5q34–35, 7q21, 10q24, 20q13, Xp22.13, Xp11.4, and Xq25 are also of importance because of their linkage to multiple trait pairs. For example, linkage to chromosome 10q24 was found for TBLM × W (LOD = 2.31), TBLM × CT (LOD = 2.51), TBLM × CSA (LOD = 2.51), TBLM × BR (LOD = 2.64), and TBLM × Z (LOD = 2.55) in women.

Conclusions: In this study, we identified several genomic regions (e.g., 3q12 and 20q13) that seem to be linked to both FNCS–GPs and TBLM. These regions are of interesting because they may harbor genes that may contribute to variation in both FNCS-GPs and TBLM.

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