A Bivariate Whole Genome Linkage Study Identified Genomic Regions Influencing Both BMD and Bone Structure

Authors

  • Xiao-Gang Liu,

    1. 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, Shaanxi, China
    2. School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri, USA
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  • Yong-Jun Liu,

    1. School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri, USA
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  • Jianfeng Liu,

    1. School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri, USA
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  • Yufang Pei,

    1. 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, Shaanxi, China
    2. School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri, USA
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  • Dong-Hai Xiong,

    1. Osteoporosis Research Center and Department of Biomedical Sciences, Creighton University, Omaha, Nebraska, USA
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  • Hui Shen,

    1. School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri, USA
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  • Hong-Yi Deng,

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

    1. School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri, USA
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  • Betty M Drees,

    1. School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri, USA
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  • James J Hamilton,

    1. School of Medicine, 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, Omaha, Nebraska, USA
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  • Hong-Wen Deng

    Corresponding author
    1. 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, Shaanxi, China
    2. School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri, USA
    3. Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China
    • Address reprint requests to: Hong-Wen Deng, PhD, 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, Shaanxi 710049, China
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  • The authors state that they have no conflicts of interest.

Abstract

Areal BMD (aBMD) and areal bone size (ABS) are biologically correlated traits and are each important determinants of bone strength and risk of fractures. Studies showed that aBMD and ABS are genetically correlated, indicating that they may share some common genetic factors, which, however, are largely unknown. To study the genetic factors influencing both aBMD and ABS, bivariate whole genome linkage analyses were conducted for aBMD-ABS at the femoral neck (FN), lumbar spine (LS), and ultradistal (UD)-forearm in a large sample of 451 white pedigrees made up of 4498 individuals. We detected significant linkage on chromosome Xq27 (LOD = 4.89) for LS aBMD-ABS. In addition, we detected suggestive linkages at 20q11 (LOD = 3.65) and Xp11 (LOD = 2.96) for FN aBMD-ABS; at 12p11 (LOD = 3.39) and 17q21 (LOD = 2.94) for LS aBMD-ABS; and at 5q23 (LOD = 3.54), 7p15 (LOD = 3.45), Xq27 (LOD = 2.93), and 12p11 (LOD = 2.92) for UD-forearm aBMD-ABS. Subsequent discrimination analyses indicated that quantitative trait loci (QTLs) at 12p11 and 17q21 may have pleiotropic effects on aBMD and ABS. This study identified several genomic regions that may contain QTLs important for both aBMD and ABS. Further endeavors are necessary to follow these regions to eventually pinpoint the genetic variants affecting bone strength and risk of fractures.

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