Bivariate Whole Genome Linkage Analyses for Total Body Lean Mass and BMD

Authors

  • Xiang-Li Wang,

    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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  • 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
    2. Departments of Orthopaedic Surgery and Basic Medical Sciences, University of Missouri–Kansas City, Kansas City, Missouri, USA
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  • Li-Jun Tan,

    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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  • Hong-Yi Deng,

    1. Departments of Orthopaedic Surgery and Basic Medical Sciences, University of Missouri–Kansas City, Kansas City, Missouri, USA
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  • Yao-Zhong Liu,

    1. Departments of Orthopaedic Surgery and Basic Medical Sciences, University of Missouri–Kansas City, Kansas City, Missouri, USA
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  • Christopher J Papasian,

    1. Departments of Orthopaedic 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. Departments of Orthopaedic Surgery and Basic Medical Sciences, University of Missouri–Kansas City, Kansas City, Missouri, USA
    3. 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, Shanxi, China
    • Laboratory of Molecular and Statistical Genetics and the Key Laboratory of Protein Chemistry and Developmental Biology, Ministry of Education, 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.

Abstract

A genome-wide bivariate analysis was conducted for TBLM and BMD at the spine and hip in a large white sample. We found some QTLs shared by TBLM and BMD in the entire sample and the sex-specific subgroups, and QTLs with potential pleiotropy were disclosed.

Introduction: Previous studies suggested that total body lean mass (TBLM) and BMD are highly genetically correlated. However, the specific shared genetic factors between TBLM and BMD are unknown.

Materials and Methods: To identify the specific quantitative trait loci (QTLs) shared by TBLM and BMD at the spine (L1–L4) and total hip, we performed bivariate whole genome linkage analysis (WGLA) in a large sample involving 4498 white subjects of European origin.

Results: Multipoint bivariate linkage analyses for 22 autosomes showed evidence of significant linkage with an LOD score of 4.86 at chromosome region 15q13 for TBLM and spine BMD in women, and suggestive linkage findings (LOD > 2.2) at 7p22 for TBLM and spine BMD for the entire sample, at 7q32 for TBLM and BMD at both spine and hip in women, and at 7q21 and 13p11 for TBLM and BMD at both spine and hip in men. Two-point linkage analyses for chromosome X also showed significant linkage signals at several regions such as Xq25. Complete pleiotropy (a single locus influencing both traits) was suggested at 7q32 and 13q11 for TBLM and BMD. Additionally, complete co-incident linkage (separate tightly clustered loci each influencing a single trait) was detected at 7p22 for TBLM and spine BMD.

Conclusions: We identified several genomic regions shared by TBLM and BMD in whites. Further studies may focus on fine mapping and identification of the specific QTLs in these candidate genomic regions.

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