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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture
Authors :
Estrada, Karol Styrkarsdottir, Unnur Evangelou, Evangelos Hsu, Yi-Hsiang Duncan, Emma L. Ntzani, Evangelia E. Oei, Ling Albagha, Omar M. E. Amin, Najaf Kemp, John P. Koller, Daniel L. Li, Guo Liu, Ching-Ti Minster, Ryan L. Moayyeri, Alireza Vandenput, Liesbeth Willner, Dana Xiao, Su-Mei Yerges-Armstrong, Laura M. Zheng, Hou-Feng Alonso, Nerea Eriksson, Joel Kammerer, Candace M. Kaptoge, Stephen K. Leo, Paul J. Thorleifsson, Gudmar Wilson, Scott G. Wilson, James F. Aalto, Ville Alen, Markku Aragaki, Aaron K. Aspelund, Thor Center, Jacqueline R. Dailiana, Zoe Duggan, David J. Garcia, Melissa Garcia-Giralt, Natalia Giroux, Sylvie Hallmans, Goran Hocking, Lynne J. Husted, Lise Bjerre Jameson, Karen A. Khusainova, Rita Kim, Ghi Su Kooperberg, Charles Koromila, Theodora Kruk, Marcin Laaksonen, Marika Lacroix, Andrea Z. Lee, Seung Hun Leung, Ping C. Lewis, Joshua R. Masi, Laura Mencej-Bedrac, Simona Nguyen, Tuan V. Nogues, Xavier Patel, Millan S. Prezelj, Janez Rose, Lynda M. Scollen, Serena Siggeirsdottir, Kristin Smith, Albert V. Svensson, Olle Trompet, Stella Trummer, Olivia van Schoor, Natasja M. Woo, Jean Zhu, Kun Balcells, Susana Brandi, Maria Luisa Buckley, Brendan M. Cheng, Sulin Christiansen, Claus Cooper, Cyrus Dedoussis, George Ford, Ian Frost, Morten Goltzman, David Gonzalez-Macias, Jesus Kahonen, Mika Karlsson, Magnus Khusnutdinova, Elza Koh, Jung-Min Kollia, Panagoula Langdahl, Bente Lomholt Leslie, William D. Lips, Paul Ljunggren, Östen Lorenc, Roman S. Marc, Janja Mellstrom, Dan Obermayer-Pietsch, Barbara Olmos, Jose M. Pettersson-Kymmer, Ulrika Reid, David M. Riancho, Jose A. Ridker, Paul M. Rousseau, Francois Slagboom, P. Eline Tang, Nelson L. S. Urreizti, Roser Van Hul, Wim Viikari, Jorma Zarrabeitia, Maria T. Aulchenko, Yurii S. Castano-Betancourt, Martha Grundberg, Elin Herrera, Lizbeth Ingvarsson, Thorvaldur Johannsdottir, Hrefna Kwan, Tony Li, Rui Luben, Robert Medina-Gomez, Carolina Palsson, Stefan Th Reppe, Sjur Rotter, Jerome I. Sigurdsson, Gunnar van Meurs, Joyce B. J. Verlaan, Dominique Williams, Frances M. K. Wood, Andrew R. Zhou, Yanhua Gautvik, Kaare M. Pastinen, Tomi Raychaudhuri, Soumya Cauley, Jane A. Chasman, Daniel I. Clark, Graeme R. Cummings, Steven R. Danoy, Patrick Dennison, Elaine M. Eastell, Richard Eisman, John A. Gudnason, Vilmundur Hofman, Albert Jackson, Rebecca D. Jones, Graeme Jukema, J. Wouter Khaw, Kay-Tee Lehtimaki, Terho Liu, Yongmei Lorentzon, Mattias McCloskey, Eugene Mitchell, Braxton D. Nandakumar, Kannabiran Nicholson, Geoffrey C. Oostra, Ben A. Peacock, Munro Pols, Huibert A. P. Prince, Richard L. Raitakari, Olli Reid, Ian R. Robbins, John Sambrook, Philip N. Sham, Pak Chung Shuldiner, Alan R. Tylavsky, Frances A. van Duijn, Cornelia M. Wareham, Nick J. Cupples, L. Adrienne Econs, Michael J. Evans, David M. Harris, Tamara B. Kung, Annie Wai Chee Psaty, Bruce M. Reeve, Jonathan Spector, Timothy D. Streeten, Elizabeth A. Zillikens, M. Carola Thorsteinsdottir, Unnur Ohlsson, Claes Karasik, David Richards, J. Brent Brown, Matthew A. Stefansson, Kari Uitterlinden, Andre G. Ralston, Stuart H. Ioannidis, John P. A. Kiel, Douglas P. Rivadeneira, Fernando Estrada, Karol Styrkarsdottir, Unnur Evangelou, Evangelos Hsu, Yi-Hsiang Duncan, Emma L. Ntzani, Evangelia E. Oei, Ling Albagha, Omar M. E. Amin, Najaf Kemp, John P. Koller, Daniel L. Li, Guo Liu, Ching-Ti Minster, Ryan L. Moayyeri, Alireza Vandenput, Liesbeth Willner, Dana Xiao, Su-Mei Yerges-Armstrong, Laura M. Zheng, Hou-Feng Alonso, Nerea Eriksson, Joel Kammerer, Candace M. Kaptoge, Stephen K. Leo, Paul J. Thorleifsson, Gudmar Wilson, Scott G. Wilson, James F. Aalto, Ville Alen, Markku Aragaki, Aaron K. Aspelund, Thor Center, Jacqueline R. Dailiana, Zoe Duggan, David J. Garcia, Melissa Garcia-Giralt, Natalia Giroux, Sylvie Hallmans, Goran Hocking, Lynne J. Husted, Lise Bjerre Jameson, Karen A. Khusainova, Rita Kim, Ghi Su Kooperberg, Charles Koromila, Theodora Kruk, Marcin Laaksonen, Marika Lacroix, Andrea Z. Lee, Seung Hun Leung, Ping C. Lewis, Joshua R. Masi, Laura Mencej-Bedrac, Simona Nguyen, Tuan V. Nogues, Xavier Patel, Millan S. Prezelj, Janez Rose, Lynda M. Scollen, Serena Siggeirsdottir, Kristin Smith, Albert V. Svensson, Olle Trompet, Stella Trummer, Olivia van Schoor, Natasja M. Woo, Jean Zhu, Kun Balcells, Susana Brandi, Maria Luisa Buckley, Brendan M. Cheng, Sulin Christiansen, Claus Cooper, Cyrus Dedoussis, George Ford, Ian Frost, Morten Goltzman, David Gonzalez-Macias, Jesus Kahonen, Mika Karlsson, Magnus Khusnutdinova, Elza Koh, Jung-Min Kollia, Panagoula Langdahl, Bente Lomholt Leslie, William D. Lips, Paul Ljunggren, Östen Lorenc, Roman S. Marc, Janja Mellstrom, Dan Obermayer-Pietsch, Barbara Olmos, Jose M. Pettersson-Kymmer, Ulrika Reid, David M. Riancho, Jose A. Ridker, Paul M. Rousseau, Francois Slagboom, P. Eline Tang, Nelson L. S. Urreizti, Roser Van Hul, Wim Viikari, Jorma Zarrabeitia, Maria T. Aulchenko, Yurii S. Castano-Betancourt, Martha Grundberg, Elin Herrera, Lizbeth Ingvarsson, Thorvaldur Johannsdottir, Hrefna Kwan, Tony Li, Rui Luben, Robert Medina-Gomez, Carolina Palsson, Stefan Th Reppe, Sjur Rotter, Jerome I. Sigurdsson, Gunnar van Meurs, Joyce B. J. Verlaan, Dominique Williams, Frances M. K. Wood, Andrew R. Zhou, Yanhua Gautvik, Kaare M. Pastinen, Tomi Raychaudhuri, Soumya Cauley, Jane A. Chasman, Daniel I. Clark, Graeme R. Cummings, Steven R. Danoy, Patrick Dennison, Elaine M. Eastell, Richard Eisman, John A. Gudnason, Vilmundur Hofman, Albert Jackson, Rebecca D. Jones, Graeme Jukema, J. Wouter Khaw, Kay-Tee Lehtimaki, Terho Liu, Yongmei Lorentzon, Mattias McCloskey, Eugene Mitchell, Braxton D. Nandakumar, Kannabiran Nicholson, Geoffrey C. Oostra, Ben A. Peacock, Munro Pols, Huibert A. P. Prince, Richard L. Raitakari, Olli Reid, Ian R. Robbins, John Sambrook, Philip N. Sham, Pak Chung Shuldiner, Alan R. Tylavsky, Frances A. van Duijn, Cornelia M. Wareham, Nick J. Cupples, L. Adrienne Econs, Michael J. Evans, David M. Harris, Tamara B. Kung, Annie Wai Chee Psaty, Bruce M. Reeve, Jonathan Spector, Timothy D. Streeten, Elizabeth A. Zillikens, M. Carola Thorsteinsdottir, Unnur Ohlsson, Claes Karasik, David Richards, J. Brent Brown, Matthew A. Stefansson, Kari Uitterlinden, Andre G. Ralston, Stuart H. Ioannidis, John P. A. Kiel, Douglas P. Rivadeneira, Fernando
Publication Year :
2012
Abstract
Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 x 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 x 10(-4), Bonferroni corrected), of which six reached P < 5 x 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
Details
Database :
OAIster
Notes :
English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1235068717
Document Type :
Electronic Resource
Full Text :
https://doi.org/10.1038.ng.2249