{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T22:35:43Z","timestamp":1773873343688,"version":"3.50.1"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2012,10,8]],"date-time":"2012-10-08T00:00:00Z","timestamp":1349654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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. Although 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 versus low hip BMD (20% tails of the distributions), in two independent U.S. Caucasian samples. The first sample contained 916 unrelated subjects with extreme hip BMD Z-scores selected from a population composed of 2286 subjects. The second sample consisted of 400 unrelated subjects with extreme hip BMD Z-scores selected from a population composed of 1000 subjects. Combining results from these two samples, we found one interacting gene pair (RBMS3 versus ZNF516) which, even after Bonferroni correction for multiple testing, showed consistently significant effects on hip BMD. RMBS3 harbored two single-nucleotide polymorphisms (SNPs), rs6549904 and rs7640046, both of which had significant interactions with an SNP, rs4891159, located on ZNF516 (p\u2009=\u20097.04\u2009\u00d7\u200910\u221211 and 1.03\u2009\u00d7\u200910\u221210). We further validated these results in two additional samples of Caucasian and African descent. The gene pair, RBMS3 versus ZNF516, was successfully replicated in the Caucasian sample (p\u2009=\u20098.07\u2009\u00d7\u200910\u22123 and 2.91\u2009\u00d7\u200910\u22123). For the African sample, a significant interaction was also detected (p\u2009=\u20090.031 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 delineates the genetic architecture of osteoporosis. \u00a9 2013 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.1788","type":"journal-article","created":{"date-parts":[[2012,10,8]],"date-time":"2012-10-08T18:41:16Z","timestamp":1349721676000},"page":"828-837","source":"Crossref","is-referenced-by-count":26,"title":["Gene-gene interaction between <i>RBMS3<\/i> and <i>ZNF516<\/i> influences bone mineral density"],"prefix":"10.1093","volume":"28","author":[{"given":"Tie-Lin","family":"Yang","sequence":"first","affiliation":[{"name":"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, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Guo","sequence":"additional","affiliation":[{"name":"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, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Li","sequence":"additional","affiliation":[{"name":"School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center of Systematic Biomedical Research, University of Shanghai for Science and Technology, Shanghai, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Shen","sequence":"additional","affiliation":[{"name":"School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyang M","family":"Li","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Missouri\u2013Kansas City, Kansas City, MO, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyuan K","family":"Li","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Missouri\u2013Kansas City, Kansas City, MO, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Tian","sequence":"additional","affiliation":[{"name":"School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong-Jun","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher J","family":"Papasian","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Missouri\u2013Kansas City, Kansas City, MO, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong-Wen","family":"Deng","sequence":"additional","affiliation":[{"name":"Center of Systematic Biomedical Research, University of Shanghai for Science and Technology, Shanghai, P.R. China"},{"name":"School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2012,10,8]]},"reference":[{"issue":"1","key":"2024020318410688000_bib1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1359\/jbmr.1997.12.1.24","article-title":"Medical expenditures for the treatment of osteoporotic fractures in the United States in 1995: report from the National Osteoporosis Foundation","volume":"12","author":"Ray","year":"1997","journal-title":"J Bone Miner Res."},{"issue":"7","key":"2024020318410688000_bib2","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1359\/JBMR.050304","article-title":"Predictive value of BMD for hip and other fractures","volume":"20","author":"Johnell","year":"2005","journal-title":"J Bone Miner 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