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In a genome-wide association study of BMD among 20,100 Icelanders, with follow-up in 10,091 subjects of European and East-Asian descent, we found a new BMD locus that harbours the <jats:italic>PTCH1<\/jats:italic> gene, represented by rs28377268 (freq. 11.4\u201322.6%) that associates with reduced spine BMD (<jats:italic>P<\/jats:italic>=1.0 \u00d7 10<jats:sup>\u221211<\/jats:sup>, <jats:italic>\u03b2<\/jats:italic>=\u22120.09). We also identified a new spine BMD signal in <jats:italic>RSPO3<\/jats:italic>, rs577721086 (freq. 6.8%), that associates with increased spine BMD (<jats:italic>P<\/jats:italic>=6.6 \u00d7 10<jats:sup>\u221210<\/jats:sup>, <jats:italic>\u03b2<\/jats:italic>=0.14). Importantly, both variants associate with osteoporotic fractures and affect expression of the <jats:italic>PTCH1<\/jats:italic> and <jats:italic>RSPO3<\/jats:italic> genes that is in line with their influence on BMD and known biological function of these genes. Additional new BMD signals were also found at the <jats:italic>AXIN1<\/jats:italic> and <jats:italic>SOST<\/jats:italic> loci and a new lead SNP at the <jats:italic>EN1<\/jats:italic> locus.<\/jats:p>","DOI":"10.1038\/ncomms10129","type":"journal-article","created":{"date-parts":[[2016,1,6]],"date-time":"2016-01-06T10:55:24Z","timestamp":1452077724000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Sequence variants in the PTCH1 gene associate with spine bone mineral density and osteoporotic fractures"],"prefix":"10.1038","volume":"7","author":[{"given":"Unnur","family":"Styrkarsdottir","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gudmar","family":"Thorleifsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigurjon A.","family":"Gudjonsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asgeir","family":"Sigurdsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline R.","family":"Center","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Hun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuan V.","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy C.Y.","family":"Kwok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny S.W.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne C.","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Woo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping-C.","family":"Leung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beom-Jun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorunn","family":"Rafnar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lambertus A.","family":"Kiemeney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorvaldur","family":"Ingvarsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Min","family":"Koh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelson L.S.","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Eisman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus","family":"Christiansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Sigurdsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Unnur","family":"Thorsteinsdottir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kari","family":"Stefansson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,1,6]]},"reference":[{"key":"BFncomms10129_CR1","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1359\/jbmr.061113","volume":"22","author":"R Burge","year":"2007","unstructured":"Burge, R. et al. 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