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Volume 36 Issue 2
Feb.  2009
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Article Contents

Bivariate whole-genome linkage scan for bone geometry and total body fat mass

doi: 10.1016/S1673-8527(08)60095-8
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  • Corresponding author: E-mail address: hwdeng@hunnu.edu.cn (Hongwen Deng)
  • Received Date: 2008-10-06
  • Accepted Date: 2008-12-10
  • Rev Recd Date: 2008-12-01
  • Available Online: 2009-02-13
  • Publish Date: 2009-02-20
  • To quantify the genetic correlations between total body fat mass (TBFM) and femoral neck geometric parameters (FNGPs) and, if possible, to detect the specific genomic regions shared by them, bivariate genetic analysis and bivariate whole-genome linkage scan were carried out in a large Caucasian population. All the phenotypes studied were significantly controlled by genetic factors (P < 0.001) with the heritabilities ranging from 0.45 to 0.68. Significantly genetic correlations were found between TBFM and CSA (cross-section area), W (sub-periosteal diameter), Z (section modulus) and CT (cortical thickness) except between TBFM and BR (buckling ratio). The peak bivariate LOD scores were 3.23 (20q12), 2.47 (20p11), 3.19 (6q27), 1.68 (20p12), and 2.47 (7q11) for the five pairs of TBFM and BR, CSA, CT, W, and Z in the entire sample, respectively. Gender-specific bivariate linkage evidences were also found for the five pairs. 6p25 had complete pleiotropic effects on the variations of TBFM & Z in the female sub-population, and 6q27 and 17q11 had coincident linkages for TBFM & CSA and TBFM & Z in the entire population. We identified moderate genetic correlations and several shared genomic regions between TBFM and FNGPs in a large Caucasian population.
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  • [1]
    Abecasis, G.R., Cherny, S.S., Cookson, W.O. et al. Merlin–rapid analysis of dense genetic maps using sparse gene flow trees Nat. Genet., 30 (2002),pp. 97-101
    [2]
    Allison, D.B., Neale, M.C., Zannolli, R. et al. Testing the robustness of the likelihood-ratio test in a variance-component quantitative-trait loci-mapping procedure Am. J. Hum. Genet., 65 (1999),pp. 531-544
    [3]
    Almasy, L., Blangero, J. Multipoint quantitative-trait linkage analysis in general pedigrees Am. J. Hum. Genet., 62 (1998),pp. 1198-1211
    [4]
    Almasy, L., Dyer, T.D., Blangero, J. Bivariate quantitative trait linkage analysis: Pleiotropy versus co-incident linkages Genet. Epidemiol., 14 (1997),pp. 953-958
    [5]
    Ammann, P., Rizzoli, R. Bone strength and its determinants Osteoporos. Int., 14 (2003),pp. S13-S18
    [6]
    Andreasson, A., Arborelius, L., Erlanson-Albertsson, C. et al. A putative role for cytokines in the impaired appetite in depression Brain Behav. Immun., 21 (2007),pp. 147-152
    [7]
    Beck, T. Measuring the structural strength of bones with dual-energy X-ray absorptiometry: Principles, technical limitations, and future possibilities Osteoporos. Int., 14 (2003),pp. 81-88
    [8]
    Bonewald, L.F., Dallas, S.L. Role of active and latent transforming growth factor beta in bone formation J. Cell. Biochem., 55 (1994),pp. 350-357
    [9]
    Bravo, P.E., Morse, S., Borne, D.M. et al. Leptin and hypertension in obesity Vasc. Health Risk Manag., 2 (2006),pp. 163-169
    [10]
    Camp, N.J., Farnham, J.M. Correcting for multiple analyses in genomewide linkage studies Ann. Hum. Genet., 65 (2001),pp. 577-582
    [11]
    Comuzzie, A.G., Rainwater, D.L., Blangero, J. et al. Shared and unique genetic effects among seven HDL phenotypes Arterioscler. Thromb. Vasc. Biol., 17 (1997),pp. 859-864
    [12]
    Deng, F.Y., Xiao, P., Lei, S.F. et al. Bivariate whole genome linkage analysis for femoral neck geometric parameters and total body lean mass J. Bone Miner. Res., 22 (2007),pp. 808-816
    [13]
    Deng, H.W., Deng, H., Liu, Y.J. et al. A genomewide linkage scan for quantitative-trait loci for obesity phenotypes Am. J. Hum. Genet., 70 (2002),pp. 1138-1151
    [14]
    Elefteriou, F., Ahn, J.D., Takeda, S. et al. Leptin regulation of bone resorption by the sympathetic nervous system and CART Nature, 434 (2005),pp. 514-520
    [15]
    Gerhardt, C.C., Romero, I.A., Cancello, R. et al. Chemokines control fat accumulation and leptin secretion by cultured human adipocytes Mol. Cell. Endocrinol., 175 (2001),pp. 81-92
    [16]
    Goulding, A., Gold, E., Cannan, R. et al. Changing femoral geometry in growing girls: A cross-sectional DEXA study Bone, 19 (1996),pp. 645-649
    [17]
    Kissebah, A.H., Krakower, G.R. Regional adiposity and morbidity Physiol. Rev., 74 (1994),pp. 761-811
    [18]
    Lander, E., Kruglyak, L. Genetic dissection of complex traits: Guidelines for interpreting and reporting linkage results Nat. Genet., 11 (1995),pp. 241-247
    [19]
    Lorentzon, M., Landin, K., Mellstrom, D. et al. Leptin is a negative independent predictor of areal BMD and cortical bone size in young adult Swedish men J. Bone Miner. Res., 21 (2006),pp. 1871-1878
    [20]
    Masinde, G.L., Li, X., Gu, W. et al. Quantitative trait loci for bone density in mice: The genes determining total skeletal density and femur density show little overlap in F2 mice Calcif. Tissue Int., 71 (2002),pp. 421-428
    [21]
    , Beck, T.J., Amin, S., Khosla, S. et al. Contributions of bone density and structure to fracture risk assessment in men and women Osteoporos. Int., 16 (2005),pp. 460-467
    [22]
    Nelson, D.A., Barondess, D.A., Hendrix, S.L. et al. Cross-sectional geometry, bone strength, and bone mass in the proximal femur in black and white postmenopausal women J. Bone Miner. Res., 15 (2000),pp. 1992-1997
    [23]
    O'Connell, J.R., Weeks, D.E. PedCheck: A program for identification of genotype incompatibilities in linkage analysis Am. J. Hum. Genet., 63 (1998),pp. 259-266
    [24]
    Pulkkinen, P., Partanen, J., Jalovaara, P. et al. Combination of bone mineral density and upper femur geometry improves the prediction of hip fracture Osteoporos. Int., 15 (2004),pp. 274-280
    [25]
    Rosen, C.J., Bouxsein, M.L. Mechanisms of disease: Is osteoporosis the obesity of bone? Nat. Clin. Pract. Rheumatol., 2 (2006),pp. 35-43
    [26]
    Semanick, L.M., Beck, T.J., Cauley, J.A. et al. Association of body composition and physical activity with proximal femur geometry in middle-aged and elderly Afro-Caribbean men: The Tobago bone health study Calcif. Tissue Int., 77 (2005),pp. 160-166
    [27]
    Shen, H., Long, J.R., Xiong, D.H. et al. A genomewide scan for quantitative trait loci underlying areal bone size variation in 451 Caucasian families J. Med. Genet., 43 (2006),pp. 873-880
    [28]
    Shen, H., Long, J.R., Xiong, D.H. et al. Mapping quantitative trait loci for cross-sectional geometry at the femoral neck J. Bone Miner. Res., 20 (2005),pp. 1973-1982
    [29]
    Stone, K.L., Seeley, D.G., Lui, L.Y. et al. BMD at multiple sites and risk of fracture of multiple types: Long-term results from the study of osteoporotic fractures J. Bone Miner. Res., 18 (2003),pp. 1947-1954
    [30]
    Sun, X., Lei, S.F., Deng, F.Y. et al. Genetic and environmental correlations between bone geometric parameters and body compositions Calcif. Tissue Int., 79 (2006),pp. 43-49
    [31]
    Tang, Z.H., Xiao, P., Lei, S.F. et al. A bivariate whole-genome linkage scan suggests several shared genomic regions for obesity and osteoporosis J. Clin. Endocrinol. Metab., 92 (2007),pp. 2751-2757
    [32]
    Wardlaw, G.M. Putting body weight and osteoporosis into perspective Am. J. Clin. Nutr., 63 (1996),pp. 433S-436S
    [33]
    Williams, J.T., Begleiter, H., Porjesz, B. et al. Joint multipoint linkage analysis of multivariate qualitative and quantitative traits. II. Alcoholism and event-related potentials Am. J. Hum. Genet., 65 (1999),pp. 1148-1160
    [34]
    Xiao, P., Shen, H., Guo, Y.F. et al. Genomic regions identified for BMD in a large sample including epistatic interactions and gender-specific effects J. Bone Miner. Res., 21 (2006),pp. 1536-1544
    [35]
    Xiong, D.H., Shen, H., Xiao, P. et al. Genome-wide scan identified QTLs underlying femoral neck cross-sectional geometry that are novel studied risk factors of osteoporosis J. Bone Miner. Res., 21 (2006),pp. 424-437
    [36]
    Zeng, Q., Li, X., Beck, G. et al. Bone, 40 (2007),pp. 374-381
    [37]
    Zeng, Q., Li, X., Choi, L. et al. Connect. Tissue Res., 47 (2006),pp. 264-270
    [38]
    Zhao, L.J., Jiang, H., Papasian, C.J. et al. Correlation of obesity and osteoporosis: Effect of fat mass on the determination of osteoporosis J. Bone Miner. Res., 23 (2008),pp. 17-29
    [39]
    Zhao, L.J., Xiao, P., Liu, Y.J. et al. A genome-wide linkage scan for quantitative trait loci underlying obesity related phenotypes in 434 Caucasian families Hum. Genet., 121 (2007),pp. 145-148
    [40]
    Zhou, S., Eid, K., Glowacki, J. Cooperation between TGF-beta and Wnt pathways during chondrocyte and adipocyte differentiation of human marrow stromal cells J. Bone Miner. Res., 19 (2004),pp. 463-470
    [41]
    Zhou, S., Lechpammer, S., Greenberger, J.S. et al. Hypoxia inhibition of adipocytogenesis in human bone marrow stromal cells requires transforming growth factor-beta/Smad3 signaling J. Biol. Chem., 280 (2005),pp. 22688-22696
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