Gene-set Based Genome-wide Association Analysis for the Speed of Sound in Two Skeletal Sites of Korean Women

Overview

Journal BMB Rep

Specialties Biochemistry
Molecular Biology

Date 2013 Nov 30

PMID 24286325

Authors

Ji-Sun Kwon

Sangsoo Kim

Affiliations

Soon will be listed here.

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.

References

Zhang Y, Seshadri S, Ellison R, Heeren T, Felson D . Bone mineral density and verbal memory impairment: Third National Health and Nutrition Examination Survey. Am J Epidemiol. 2001; 154(9):795-802. DOI: 10.1093/aje/154.9.795. View

Wan L, Zou W, Gao D, Inuzuka H, Fukushima H, Berg A . Cdh1 regulates osteoblast function through an APC/C-independent modulation of Smurf1. Mol Cell. 2011; 44(5):721-33. PMC: 3240853. DOI: 10.1016/j.molcel.2011.09.024. View

Fridley B, Biernacka J . Gene set analysis of SNP data: benefits, challenges, and future directions. Eur J Hum Genet. 2011; 19(8):837-43. PMC: 3172936. DOI: 10.1038/ejhg.2011.57. View

Sun L, Adebanjo O, Moonga B, Corisdeo S, Anandatheerthavarada H, Biswas G . CD38/ADP-ribosyl cyclase: A new role in the regulation of osteoclastic bone resorption. J Cell Biol. 1999; 146(5):1161-72. PMC: 2169484. DOI: 10.1083/jcb.146.5.1161. View

Greenblatt M, Shim J, Glimcher L . Mitogen-activated protein kinase pathways in osteoblasts. Annu Rev Cell Dev Biol. 2013; 29:63-79. DOI: 10.1146/annurev-cellbio-101512-122347. View

Wang K, Li M, Hakonarson H . Analysing biological pathways in genome-wide association studies. Nat Rev Genet. 2010; 11(12):843-54. DOI: 10.1038/nrg2884. View

Chellaiah M, Soga N, Swanson S, McAllister S, Alvarez U, Wang D . Rho-A is critical for osteoclast podosome organization, motility, and bone resorption. J Biol Chem. 2000; 275(16):11993-2002. DOI: 10.1074/jbc.275.16.11993. View

Vanoevelen J, Janssens A, Huitema L, Hammond C, Metz J, Flik G . Trpv5/6 is vital for epithelial calcium uptake and bone formation. FASEB J. 2011; 25(9):3197-207. DOI: 10.1096/fj.11-183145. View

Arai F, Ohneda O, Miyamoto T, Zhang X, Suda T . Mesenchymal stem cells in perichondrium express activated leukocyte cell adhesion molecule and participate in bone marrow formation. J Exp Med. 2002; 195(12):1549-63. PMC: 2193567. DOI: 10.1084/jem.20011700. View

10.

Gartland A, Skarratt K, Hocking L, Parsons C, Stokes L, Jorgensen N . 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. 2012; 20(5):559-64. PMC: 3330223. DOI: 10.1038/ejhg.2011.245. View

11.

Mocsai A, Humphrey M, Van Ziffle J, Hu Y, Burghardt A, Spusta S . 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. 2004; 101(16):6158-63. PMC: 395939. DOI: 10.1073/pnas.0401602101. View

12.

Cheng H, Feng J, Figueiredo M, Zhang H, Nelson P, Marigo V . Transient receptor potential melastatin type 7 channel is critical for the survival of bone marrow derived mesenchymal stem cells. Stem Cells Dev. 2009; 19(9):1393-403. PMC: 3128316. DOI: 10.1089/scd.2009.0262. View

13.

Wei Z, Tong B, Xia Y, Lu Q, Chou G, Wang Z . Norisoboldine suppresses osteoclast differentiation through preventing the accumulation of TRAF6-TAK1 complexes and activation of MAPKs/NF-κB/c-Fos/NFATc1 Pathways. PLoS One. 2013; 8(3):e59171. PMC: 3594163. DOI: 10.1371/journal.pone.0059171. View

14.

Mullin B, Prince R, Mamotte C, Spector T, Hart D, Dudbridge F . Further genetic evidence suggesting a role for the RhoGTPase-RhoGEF pathway in osteoporosis. Bone. 2009; 45(2):387-91. DOI: 10.1016/j.bone.2009.04.254. View

15.

Barrett-Connor E, Siris E, Wehren L, Miller P, Abbott T, Berger M . Osteoporosis and fracture risk in women of different ethnic groups. J Bone Miner Res. 2005; 20(2):185-94. DOI: 10.1359/JBMR.041007. View

16.

Takito J, Nakamura M . Precursors linked via the zipper-like structure or the filopodium during the secondary fusion of osteoclasts. Commun Integr Biol. 2012; 5(5):453-7. PMC: 3502206. DOI: 10.4161/cib.20980. View

17.

Nam D, Kim J, Kim S, Kim S . GSA-SNP: a general approach for gene set analysis of polymorphisms. Nucleic Acids Res. 2010; 38(Web Server issue):W749-54. PMC: 2896081. DOI: 10.1093/nar/gkq428. View

18.

Mathews S, Bhonde R, Gupta P, Totey S . Extracellular matrix protein mediated regulation of the osteoblast differentiation of bone marrow derived human mesenchymal stem cells. Differentiation. 2012; 84(2):185-92. DOI: 10.1016/j.diff.2012.05.001. View

19.

Boonrungsiman S, Gentleman E, Carzaniga R, Evans N, McComb D, Porter A . The role of intracellular calcium phosphate in osteoblast-mediated bone apatite formation. Proc Natl Acad Sci U S A. 2012; 109(35):14170-5. PMC: 3435222. DOI: 10.1073/pnas.1208916109. View

20.

Abed E, Moreau R . Importance of melastatin-like transient receptor potential 7 and cations (magnesium, calcium) in human osteoblast-like cell proliferation. Cell Prolif. 2007; 40(6):849-65. PMC: 6495302. DOI: 10.1111/j.1365-2184.2007.00476.x. View