Browse > Article
http://dx.doi.org/10.5483/BMBRep.2014.47.6.181

Gene-set based genome-wide association analysis for the speed of sound in two skeletal sites of Korean women  

Kwon, Ji-Sun (Department of Bioinformatics and Life Science, Soongsil University)
Kim, Sangsoo (Department of Bioinformatics and Life Science, Soongsil University)
Publication Information
BMB Reports / v.47, no.6, 2014 , pp. 348-353 More about this Journal
Abstract
The speed of sound (SOS) value is an indicator of bone mineral density (BMD). Previous genome-wide association (GWA) studies have identified a number of genes, whose variations may affect BMD levels. However, their biological implications have been elusive. We re-analyzed the GWA study dataset for the SOS values in skeletal sites of 4,659 Korean women, using a gene-set analysis software, GSA-SNP. We identified 10 common representative GO terms, and 17 candidate genes between these two traits (PGS < 0.05). Implication of these GO terms and genes in the bone mechanism is well supported by the literature survey. Interestingly, the significance levels of some member genes were inversely related, in several gene-sets that were shared between two skeletal sites. This implies that biological process, rather than SNP or gene, is the substantial unit of genetic association for SOS in bone. In conclusion, our findings may provide new insights into the biological mechanisms for BMD.
Keywords
Bone mineral density; Gene ontology; Gene-set analysis; GWAS; Speed of sound;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Abed, E. and Moreau, R. (2007) Importance of melastatin-like transient receptor potential 7 and cations (magnesium, calcium) in human osteoblast-like cell proliferation. Cell Prolif. 40, 849-865.   DOI   ScienceOn
2 Cheng, H., Feng, J.M., Figueiredo, M.L., Zhang, H., Nelson, P.L., Marigo, V. and Beck, A. (2010) Transient receptor potential melastatin type 7 channel is critical for the survival of bone marrow derived mesenchymal stem cells. Stem Cells Dev. 19, 1393-1403.   DOI   ScienceOn
3 Boonrungsiman, S., Gentleman, E., Carzaniga, R., Evans, N. D., McComb, D. W., Porter, A. E. and Stevens, M. M. (2012) The role of intracellular calcium phosphate in osteoblast-mediated bone apatite formation. Proc. Natl. Acad. Sci. U. S. A. 109, 14170-14175.   DOI
4 Blair, H. C., Schlesinger, P. H., Huang, C. L. and Zaidi, M. (2007) Calcium signalling and calcium transport in bone disease. Subcell Biochem. 45, 539-562.   DOI
5 Chellaiah, M. A., Soga, N., Swanson, S., McAllister, S., Alvarez, U., Wang, D., Dowdy, S. F. and Hruska, K. A. (2000) Rho-A is critical for osteoclast podosome organization, motility, and bone resorption. J. Biol. Chem. 275, 11993-12002.   DOI   ScienceOn
6 Mullin, B. H., Prince, R. L., Mamotte, C., Spector, T. D., Hart, D. J., Dudbridge, F. and Wilson, S. G. (2009) Further genetic evidence suggesting a role for the RhoGTPase-RhoGEF pathway in osteoporosis. Bone 45, 387-391.   DOI   ScienceOn
7 Jones, K. B., Mollano, A. V., Morcuende, J. A., Cooper, R. R. and Saltzman, C. L. (2004) Bone and brain: a review of neural, hormonal, and musculoskeletal connections. Iowa Orthop. J. 24, 123-132.
8 Low, Y. L., Li, Y., Humphreys, K., Thalamuthu, A., Li, Y., Darabi, H., Wedren, S., Bonnard, C., Czene, K., Iles, M. M., Heikkinen, T., Aittomaki, K., Blomqvist, C., Nevanlinna, H., Hall, P., Liu, E. T. and Liu, J. (2010) Multi-variant pathway association analysis reveals the importance of genetic determinants of estrogen metabolism in breast and endometrial cancer susceptibility. PLoS Genet. 6, e1001012.   DOI   ScienceOn
9 Fridley, B. L. and Biernacka, J. M. (2011) Gene set analysis of SNP data: benefits, challenges, and future Directions. Eur. J. Hum. Genet. 19, 837-843.   DOI   ScienceOn
10 Nam, D., Kim, J., Kim, S. Y. and Kim, S. (2010) GSA-SNP: a general approach for gene set analysis of polymorphisms. Nucleic. Acids Res. 38, W749-754.   DOI   ScienceOn
11 Rose, E. C., Hagenmuller, M., Jonas, I. E. and Rahn, B. A. (2005) Validation of speed of sound for the assessment of cortical bone maturity. Eur. J. Orthod. 27, 190-195.   DOI   ScienceOn
12 Loskutova, N., Honea, R. A., Vidoni, E. D., Brooks, W. M. and Burns, J. M. (2009) Bone density and brain atrophy in early Alzheimer's disease. J. Alzheimers Dis. 18, 777-785.   DOI
13 Zhang, L., Guo, Y. F., Liu, Y. Z., Liu, Y. J., Xiong, D. H., Liu, X. G., Wang, L., Yang, T. L., Lei, S. F., Guo, Y., Yan, H., Pei, Y. F., Zhang, F., Papasian, C. J., Recker, R. R. and Deng, H. W. (2010) Pathway-based genome-wide association analysis identified the importance of regulation-of-autophagy pathway for ultradistal radius BMD. J. Bone Miner. Res. 25, 1572-1580.   DOI   ScienceOn
14 Lee, Y. H., Choi, S. J., Ji, J. D. and Song, G. G. (2012) Pathway analysis of genome-wide association study for bone mineral density. Mol. Biol. Rep. 39, 8099-8106.   DOI   ScienceOn
15 Vanoevelen, J., Janssens, A., Huitema, L. F., Hammond, C. L., Metz, J. R., Flik, G., Voets, T. and Schulte-Merker, S. (2011) Trpv5/6 is vital for epithelial calcium uptake and bone formation. FASEB J. 25, 3197-3207.   DOI   ScienceOn
16 Arai, F., Ohneda, O., Miyamoto, T., Zhang, X. Q. and Suda, T. (2002) Mesenchymal stem cells in perichondrium express activated leukocyte cell adhesion molecule and participate in bone marrow formation. J. Exp. Med. 195, 1549-1563.   DOI   ScienceOn
17 Sun, L., Adebanjo, O. A., Moonga, B. S., Corisdeo, S., Anandatheerthavarada, H. K., Biswas, G., Arakawa, T., Hakeda, Y., Koval, A., Sodam, B., Bevis, P. J., Moser, A. J., Lai, F. A., Epstein, S., Troen, B. R., Kumegawa, M. and Zaidi, M. (1999) CD38/ADP-ribosyl cyclase: A new role in the regulation of osteoclastic bone resorption. J. Cell Biol. 146, 1161-1172.   DOI
18 Wei, Z. F., Tong, B., Xia, Y. F., Lu, Q., Chou, G. X., Wang, Z. T. and Dai, Y. (2013) Norisoboldine suppresses osteoclast differentiation through preventing the accumulation of TRAF6-TAK1 complexes and activation of MAPKs/NF-${\kappa}B$/c-Fos/NFATc1 Pathways. PLoS One 8, e59171.   DOI
19 Zhang, Y., Seshadri, S., Ellison, R. C., Heeren, T. and Felson, D. T. (2001) Bone mineral density and verbal memory impairment: Third National Health and Nutrition Examination Survey. Am. J. Epidemiol. 154, 795-802.   DOI   ScienceOn
20 Takito, J. and Nakamura, M. (2012) Precursors linked via the zipper-like structure or the filopodium during the secondary fusion of osteoclasts. Commun. Integr. Biol. 5, 453-457.   DOI
21 Wan, L., Zou, W., Gao, D., Inuzuka, H., Fukushima, H., Berg, A. H., Drapp, R., Shaik, S., Hu, D., Lester, C., Eguren, M., Malumbres, M., Glimcher, L. H. and Wei, W. (2011) Cdh1 regulates osteoblast function through an APC/C-independent modulation of Smurf1. Mol. Cell 44, 721-733.   DOI   ScienceOn
22 Marchini, J., Howie, B., Myers, S., McVean, G. and Donnelly, P. (2007) A new multipoint method for genome-wide association studies by imputation of genotypes. Nat. Genet. 39, 906-913.   DOI   ScienceOn
23 Eswarakumar, V. P., Monsonego-Ornan, E., Pines, M., Antonopoulou, I., Morriss-Kay, G. M. and Lonai, P. (2002) The IIIc alternative of Fgfr2 is a positive regulator of bone formation. Development 129, 3783-3793.
24 Mocsai, A., Humphrey, M. B., Van Ziffle, J. A., Hu, Y., Burghardt, A., Spusta, S. C., Majumdar, S., Lanier, L. L., Lowell, C. A. and Nakamura, M. C. (2004) The immunomodulatory adapter proteins DAP12 and Fc receptor gamma-chain (FcRgamma) regulate development of functional osteoclasts through the Syk tyrosine kinase. Proc. Natl. Acad. Sci. U. S. A. 101, 6158-6163.   DOI   ScienceOn
25 Bosetti, M., Leigheb, M., Brooks, R. A., Boccafoschi, F. and Cannas, M. F. (2010) Regulation of osteoblast and osteoclast functions by FGF-6. J. Cell Physiol. 225, 466-471.   DOI   ScienceOn
26 Lecanda, F., Cheng, S. L., Shin, C. S., Davidson, M. K., Warlow, P., Avioli, L. V. and Civitelli, R. (2000) Differential regulation of cadherins by dexamethasone in human osteoblastic cells. J. Cell Biochem. 77, 499-506.   DOI
27 Greenblatt, M. B., Shim, J. H. and Glimcher, L. H. (2013) Mitogen-activated protein kinase pathways in osteoblasts. Annu. Rev. Cell Dev. Biol.
28 Gartland, A., Skarratt, K. K., Hocking, L. J., Parsons, C., Stokes, L., Jorgensen, N. R., Fraser, W. D., Reid, D. M., Gallagher, J. A. and Wiley, J. S. (2012) Polymorphisms in the P2X7 receptor gene are associated with low lumbar spine bone mineral density and accelerated bone loss in post-menopausal women. Eur. J. Hum. Genet. 20, 559-564.   DOI   ScienceOn
29 Loi, A., Lisci, S., Denotti, A. and Cauli, A. (2013) Bone mineral density in women on long-term mud-bath therapy in a Salus per Aquam (SPA) environment. Reumatismo 65, 121-125.
30 Barrett-Connor, E., Siris, E. S., Wehren, L. E., Miller, P. D., Abbott, T. A., Berger, M. L., Santora, A. C. and Sherwood, L. M. (2005) Osteoporosis and fracture risk in women of different ethnic groups. J. Bone Miner. Res. 20, 185-194.
31 Lee, Y. H., Choi, S. J., Ji, J. D. and Song, G. G. (2012) Pathway analysis of genome-wide association study for bone mineral density. Mol. Biol. Rep. 39, 8099-8106.   DOI   ScienceOn
32 Wang, K., Li, M. and Hakonarson, H. (2010) Analysing biological pathways in genome-wide association studies. Nat. Rev. Genet., 11, 843-854.   DOI   ScienceOn
33 Schadt, E. E. (2009) Molecular networks as sensors and drivers of common human diseases. Nature 461, 218-223.   DOI   ScienceOn
34 Cho, Y. S., Go, M. J., Kim, Y. J., Heo, J. Y., Oh, J. H., Ban, H. J., Yoon, D., Lee, M. H., Kim, D. J., Park, M., Cha, S. H., Kim, J. W., Han, B. G., Min, H., Ahn, Y., Park, M. S., Han, H. R., Jang, H. Y., Cho, E. Y., Lee, J. E., Cho, N. H., Shin, C., Park, T., Park, J. W., Lee, J. K., Cardon, L., Clarke, G., McCarthy, M. I., Lee, J. Y., Lee, J. K., Oh, B. and Kim, H. L. (2009) A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits. Nat. Genet. 41, 527-534.   DOI   ScienceOn
35 Weycker, D., Macarios, D., Edelsberg, J. and Oster, G. (2007) Compliance with osteoporosis drug therapy and risk of fracture. Osteoporos. Int. 18, 271-277.   DOI   ScienceOn
36 Mathews, S., Bhonde, R., Gupta, P.K. and Totey, S. (2012) Extracellular matrix protein mediated regulation of the osteoblast differentiation of bone marrow derived human mesenchymal stem cells. Differentiation 84, 185-192.   DOI   ScienceOn