{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T04:58:50Z","timestamp":1695963530763},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,8,29]],"date-time":"2006-08-29T00:00:00Z","timestamp":1156809600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2007,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Bone mineral density (BMD) is a primary risk indicator of osteoporotic fractures, which are largely determined by the actions of multiple genes. Genetic linkage studies have seldom explored epistatic interaction of genes for BMD. To evaluate potential genetic interactions for BMD at the femoral neck (FN) we conducted a variance component linkage analysis, to test epistatic effects between the genomic region containing the <jats:italic>COL1A1<\/jats:italic> (collagen type I alpha 1) gene and the genomic regions containing genes regulating osteoclast differentiation (e.g. <jats:italic>TNFRSF11A<\/jats:italic> encoding RANK (receptor for activation of nuclear factor kappa B), <jats:italic>TNFSF11<\/jats:italic> encoding RANKL (RANK ligand), IL1A (interleukin\u20101 alpha), IL6 (interleukin\u20106), etc) in 3998 Caucasian subjects from 434 pedigrees. We detected significant epistatic interactions between the regions containing <jats:italic>COL1A1<\/jats:italic> with IL6 (p = 0.004) and <jats:italic>TNFRSF1B<\/jats:italic> encoding TNFR2 (tumor necrosis factor receptor 2) (p = 0.003), respectively. In summary, we identified the epistatic effects on BMD between regions containing several prominent candidate genes. Our results suggested that the IL6 and <jats:italic>TNFRSF1B<\/jats:italic> genes may regulate FN BMD variation through interactions with the <jats:italic>COL1A1<\/jats:italic> gene, which should be substantiated by other, or population\u2010based, association studies.<\/jats:p>","DOI":"10.1111\/j.1469-1809.2006.00313.x","type":"journal-article","created":{"date-parts":[[2006,8,29]],"date-time":"2006-08-29T11:44:12Z","timestamp":1156851852000},"page":"152-159","source":"Crossref","is-referenced-by-count":4,"title":["Epistatic Interactions between Genomic Regions Containing the <i>COL1A1<\/i> Gene and Genes Regulating Osteoclast Differentiation may Influence Femoral Neck Bone Mineral Density"],"prefix":"10.1111","volume":"71","author":[{"given":"Tie\u2010Lin","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong\u2010Hai","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan\u2010fang","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yao\u2010Zhong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert R.","family":"Recker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong\u2010Wen","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,8,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng786"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)61511-5"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1086\/301844"},{"key":"e_1_2_6_5_1","first-page":"535","article-title":"Robust variance\u2010components approach for assessing genetic linkage in pedigrees","volume":"54","author":"Amos C. 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