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Gene-gene interaction between RBMS3 and ZNF516 influences bone mineral density.
MedLine Citation:
PMID:  23045156     Owner:  NLM     Status:  Publisher    
Osteoporosis is characterized by low bone mineral density (BMD), a highly heritable trait that is determined, in part, by the actions and interactions of multiple genes. While an increasing number of genes have been identified to have independent effects on BMD, few studies have been performed to identify genes that interact with one another to affect BMD. In this study, we performed gene-gene interaction analyses in selected candidate genes in individuals with extremely high vs. low hip BMD (20% tails of the distributions), in two independent US Caucasian samples. The first sample contained 916 unrelated subjects with extreme hip BMD Z-scores selected from a population composed of 2,286 subjects. The second sample consisted of 400 unrelated subjects with extreme hip BMD Z-scores selected from a population composed of 1,000 subjects. Combining results from these two samples, we found one interacting gene pair (RBMS3 vs. ZNF516) which, even after Bonferroni correction for multiple testing, showed consistently significant effects on hip BMD. RMBS3 harbored two SNPs, rs6549904 and rs7640046, both of which had significant interactions with a SNP, rs4891159, located on ZNF516 (P values: 7.04×10(-11) and 1.03×10(-10) ). We further validated these results in two additional samples of Caucasian and African descent. The gene pair, RBMS3 vs. ZNF516, was successfully replicated in the Caucasian sample (P values: 8.07×10(-3) and 2.91×10(-3) ). For the African sample, a significant interaction was also detected (P values: 0.031 and 0.043), but the direction of the effect was opposite to that observed in the three Caucasian samples. By providing evidence for genetic interactions underlying BMD, this study further delineated the genetic architecture of osteoporosis. © 2012 American Society for Bone and Mineral Research.
Tie-Lin Yang; Yan Guo; Jian Li; Lei Zhang; Hui Shen; Siyang M Li; Siyuan K Li; Qing Tian; Yong-Jun Liu; Christopher J Papasian; Hong-Wen Deng
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-8
Journal Detail:
Title:  Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research     Volume:  -     ISSN:  1523-4681     ISO Abbreviation:  J. Bone Miner. Res.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8610640     Medline TA:  J Bone Miner Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 American Society for Bone and Mineral Research.
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 710049, P. R. China.
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