Estrada, KarolStyrkarsdottir, UnnurEvangelou, EvangelosHsu, Yi-HsiangDuncan, Emma LNtzani, Evangelia EOei, LingAlbagha, Omar M EAmin, NajafKemp, John PKoller, Daniel LLi, GuoLiu, Ching-TiMinster, Ryan LMoayyeri, AlirezaVandenput, LiesbethWillner, DanaXiao, Su-MeiYerges-Armstrong, Laura MZheng, Hou-FengAlonso, NereaEriksson, JoelKammerer, Candace MKaptoge, Stephen KLeo, Paul JThorleifsson, GudmarWilson, Scott GWilson, James FAalto, VilleAlen, MarkkuAragaki, Aaron KAspelund, ThorCenter, Jacqueline RDailiana, ZoeDuggan, David JGarcia, MelissaGarcia-Giralt, NatàliaGiroux, SylvieHallmans, GöranHocking, Lynne JHusted, Lise BjerreJameson, Karen AKhusainova, RitaKim, Ghi SuKooperberg, CharlesKoromila, TheodoraKruk, MarcinLaaksonen, MarikaLacroix, Andrea ZLee, Seung HunLeung, Ping CLewis, Joshua RMasi, LauraMencej-Bedrac, SimonaNguyen, Tuan VNogues, XavierPatel, Millan SPrezelj, JanezRose, Lynda MScollen, SerenaSiggeirsdottir, KristinSmith, Albert VSvensson, OlleTrompet, StellaTrummer, Oliviavan Schoor, Natasja MWoo, JeanZhu, KunBalcells, SusanaBrandi, Maria LuisaBuckley, Brendan MCheng, SulinChristiansen, ClausCooper, CyrusDedoussis, GeorgeFord, IanFrost, MortenGoltzman, DavidGonzález-Macías, JesúsKähönen, MikaKarlsson, MagnusKhusnutdinova, ElzaKoh, Jung-MinKollia, PanagoulaLangdahl, Bente LomholtLeslie, William DLips, PaulLjunggren, ÖstenLorenc, Roman SMarc, JanjaMellström, DanObermayer-Pietsch, BarbaraOlmos, José MPettersson-Kymmer, UlrikaReid, David MRiancho, José ARidker, PaulRousseau, FrançoisSlagboom, P ElineTang, Nelson LSUrreizti, RoserVan Hul, WimViikari, JormaZarrabeitia, María TAulchenko, Yurii SCastano-Betancourt, MarthaGrundberg, ElinHerrera, LizbethIngvarsson, ThorvaldurJohannsdottir, HrefnaKwan, TonyLi, RuiLuben, RobertMedina-Gómez, CarolinaPalsson, Stefan ThReppe, SjurRotter, Jerome ISigurdsson, Gunnarvan Meurs, Joyce B JVerlaan, DominiqueWilliams, Frances MKWood, Andrew RBird, YanhuaGautvik, Kaare MPastinen, TomiRaychaudhuri, SoumyaCauley, Jane AChasman, DanielClark, Graeme RCummings, Steven RDanoy, PatrickDennison, Elaine MEastell, RichardEisman, John AGudnason, VilmundurHofman, AlbertJackson, Rebecca DJones, GraemeJukema, J WouterKhaw, Kay-TeeLehtimäki, TerhoLiu, YongmeiLorentzon, MattiasMcCloskey, EugeneMitchell, Braxton DNandakumar, KannabiranNicholson, Geoffrey COostra, Ben APeacock, MunroPols, Huibert A PPrince, Richard LRaitakari, OlliReid, Ian RRobbins, JohnSambrook, Philip NSham, Pak ChungShuldiner, Alan RTylavsky, Frances Avan Duijn, Cornelia MWareham, Nick JCupples, L AdrienneEcons, Michael JEvans, David MHarris, Tamara BKung, Annie Wai CheePsaty, Bruce MReeve, JonathanSpector, Timothy DStreeten, Elizabeth AZillikens, M CarolaThorsteinsdottir, UnnurOhlsson, ClaesKarasik, DavidRichards, J BrentBrown, Matthew AStefansson, KariUitterlinden, André GRalston, Stuart HIoannidis, John P AKiel, DouglasRivadeneira, Fernando2013-04-222012Estrada, 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): 491-501.1061-4036http://nrs.harvard.edu/urn-3:HUL.InstRepos:10579380Bone 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.en-USJournal Article2013-04-2210.1038/ng.2249