Sequence variants in the PTCH1 gene associate with spine bone mineral density and osteoporotic fractures.

• Published in: Nature Communications
• Main Authors: Styrkarsdottir, Unnur, Thorleifsson, Gudmar, Gudjonsson, Sigurjon A, Sigurdsson, Asgeir, Center, Jacqueline R, Lee, Seung Hun, Nguyen, Tuan V, Kwok, Timothy C Y, Lee, Jenny S W, Ho, Suzanne C, Woo, Jean, Leung, Ping-C, Kim, Beom-Jun, Rafnar, Thorunn, Kiemeney, Lambertus A, Ingvarsson, Thorvaldur, Koh, Jung-Min, Tang, Nelson L S, Eisman, John A, Christiansen, Claus, Sigurdsson, Gunnar, Thorsteinsdottir, Unnur, Stefansson, Kari
• Other Authors: 1 DeCODE Genet Amgen, IS-101 Reykjavik, Iceland 2 Garvan Inst Med Res, Osteoporosis & Bone Biol, Sydney, NSW 2010, Australia 3 Univ Notre Dame Australia, Sch Med Sydney, Sydney, NSW 2010, Australia 4 St Vincents Hosp, Sch Clin, Sydney, NSW 2010, Australia 5 Univ New S Wales, Fac Med, Sydney, NSW 2010, Australia 6 Univ Ulsan, Coll Med, Asan Med Ctr, Div Endocrinol & Metab, Seoul 138736, South Korea 7 Univ Technol Sydney, Ctr Hlth Technol, Sydney, NSW 2010, Australia 8 Chinese Univ Hong Kong, Fac Med, Dept Med & Therapeut, Hong Kong, Peoples R China 9 Chinese Univ Hong Kong, Fac Med, JC Sch Publ Hlth & Primary Care, Hong Kong, Peoples R China 10 Chinese Univ Hong Kong, Fac Med, Jockey Club Ctr Osteoporosis Care & Control, Hong Kong, Peoples R China 11 Radboud Univ Nijmegen Med Ctr, Radboud Inst Hlth Sci, NL-6500 HB Nijmegen, Netherlands 12 Akureyri Hosp, Dept Orthoped Surg, IS-603 Akureyri, Iceland 13 Univ Akureyri, Inst Hlth Sci, IS-603 Akureyri, Iceland 14 Chinese Univ Hong Kong, Fac Med, Dept Chem Pathol, Hong Kong, Peoples R China 15 Chinese Univ Hong Kong, Fac Med, Li Ka Shing Inst Hlth Sci, Lab Genet Dis Susceptibil, Hong Kong, Peoples R China 16 Garvan Inst Med Res, Clin Translat & Adv Educ, Sydney, NSW 2010, Australia 17 Nord Biosci A S, DK-2730 Herlev, Denmark 18 Natl Univ Hosp Iceland, Dept Endocrinol & Metab Landspitali, IS-101 Reykjavik, Iceland Organization-Enhanced Name(s) Landspitali National University Hospital 19 Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland
• Format: Article in Journal/Newspaper
• Language: English
• Published: Nature Publishing Group 2016
• Subjects: Beinþéttni; Beinþynning; Beinbrot; Arfgengi; END12; Bone Density/genetics*; Osteoporotic Fractures; Genome-Wide Association Study; Iceland
• Online Access: http://hdl.handle.net/2336/605862; https://doi.org/10.1038/ncomms10129

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access. Bone mineral density (BMD) is a measure of osteoporosis and is useful in evaluating the risk of fracture. 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 PTCH1 gene, represented by rs28377268 (freq. 11.4-22.6%) that associates with reduced spine BMD (P=1.0 × 10(-11), β=-0.09). We also identified a new spine BMD signal in RSPO3, rs577721086 (freq. 6.8%), that associates with increased spine BMD (P=6.6 × 10(-10), β=0.14). Importantly, both variants associate with osteoporotic fractures and affect expression of the PTCH1 and RSPO3 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 AXIN1 and SOST loci and a new lead SNP at the EN1 locus. Health and Medical Research Fund/2133811 CUHK direct grant VC discretionary fund