Please use this identifier to cite or link to this item: http://dl.umsu.ac.ir/handle/Hannan/27090
Title: 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, Natàlia;Giroux, Sylvie;Hallmans, Göran;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;González-Macías, Jesús;Kähönen, 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;Mellström, Dan;Obermayer-Pietsch, Barbara;Olmos, José M;Pettersson-Kymmer, Ulrika;Reid, David M;Riancho, José A;Ridker, Paul M;Rousseau, François;Slagboom, P Eline;Tang, Nelson LS;Urreizti, Roser;Van Hul, Wim;Viikari, Jorma;Zarrabeitia, María T;Aulchenko, Yurii S;Castano-Betancourt, Martha;Grundberg, Elin;Herrera, Lizbeth;Ingvarsson, Thorvaldur;Johannsdottir, Hrefna;Kwan, Tony;Li, Rui;Luben, Robert;Medina-Gómez, Carolina;Palsson, Stefan Th;Reppe, Sjur;Rotter, Jerome I;Sigurdsson, Gunnar;van Meurs, Joyce B J;Verlaan, Dominique;Williams, Frances MK;Wood, Andrew R;Zhou, Yanhua;Gautvik, Kaare M;Pastinen, Tomi;Raychaudhuri, Soumya;Cauley, Jane A;Chasman, Daniel Ian;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;Lehtimäki, 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, André G;Ralston, Stuart H;Ioannidis, John P A;Kiel, Douglas P.;Rivadeneira, Fernando
Year: 2012
Description: Bone mineral density (BMD) is the most important 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-associated BMD markers for replication in 50,933 independent subjects and for risk of low-trauma fracture in 31,016 cases and 102,444 controls. We identified 56 loci (32 novel)associated with BMD atgenome-wide significant level (P<5×10−8). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal-stem-cell differentiation, endochondral ossification and the Wnt signalling pathways. However, we also discovered loci containing genes not known to play a role in bone biology. Fourteen BMD loci were also associated with fracture risk (P<5×10−4, Bonferroni corrected), of which six reached P<5×10−8 including: 18p11.21 (C18orf19), 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.
URI: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338864/pdf/
http://nrs.harvard.edu/urn-3:HUL.InstRepos:10579380
Standard no: Estrada, Karol, Unnur Styrkarsdottir, Evangelos Evangelou, Yi-Hsiang Hsu, Emma L Duncan, Evangelia E Ntzani, Ling Oei, et al. 2012. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nature Genetics 44(5): 491-501.
1061-4036
Appears in Collections:HMS Scholarly Articles

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