Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies.
Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies.
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DOI：
10.1038/ng.446
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发表时间：
2009-11
期刊：
影响因子：
30.8
通讯作者：
Uitterlinden, Andre G.
中科院分区：
文献类型：
--
作者：
Rivadeneira, Fernando;Styrkarsdottir, Unnur;Estrada, Karol;Halldorsson, Bjarni V.;Hsu, Yi-Hsiang;Richards, J. Brent;Zillikens, M. Carola;Kavvoura, Fotini K.;Amin, Najaf;Aulchenko, Yurii S.;Cupples, L. Adrienne;Deloukas, Panagiotis;Demissie, Serkalem;Grundberg, Elin;Hofman, Albert;Kong, Augustine;Karasik, David;van Meurs, Joyce B.;Oostra, Ben;Pastinen, Tomi;Pols, Huibert A. P.;Sigurdsson, Gunnar;Soranzo, Nicole;Thorleifsson, Gudmar;Thorsteinsdottir, Unnur;Williams, Frances M. K.;Wilson, Scott G.;Zhou, Yanhua;Ralston, Stuart H.;van Duijn, Cornelia M.;Spector, Timothy;Kiel, Douglas P.;Stefansson, Kari;Ioannidis, John P. A.;Uitterlinden, Andre G.
骨矿物质密度（BMD）是一种遗传的复杂性状，用于骨质疏松症的临床诊断和骨折风险的评估。我们对19,195名北方欧洲血统受试者的5项股骨颈和腰椎BMD全基因组关联研究进行了荟萃分析。我们确定了20个基因座达到全基因组意义（GWS; P<5×10−8），其中13个定位于新区域，包括1p31.3（GPR 177），2 p21（SPTBN 1），3 p22（CTNNB 1），4q21.1（MEPE），5 q14（MEF 2C），7 p14（STARD3NL）、7q21.3（FLJ42280）、11p11.2（LRP 4; ARHGAP 1; F2）、11p14.1（DCDC 5）、11p15（SOX 6）、16q24（FOXL1）、17q21（HDAC 5）和17q12（CRHR 1）。荟萃分析还在GWS水平证实了1 p36（ZBTB 40），6 q25（ESR 1），8 q24（TNFRSF 11B），11q13.4（LRP 5），12 q13（SP 7），13 q14（TNFSF 11）和18 q21（TNFRSF 11 A）上的7个已知BMD位点。与BMD相关的众多SNPs映射到与骨代谢相关的信号传导途径中的基因，并突出了骨质疏松症和BMD变异的复杂遗传结构。
Bone mineral density (BMD) is a heritable complex trait used in the clinical diagnosis of osteoporosis and the assessment of fracture risk. We performed meta-analysis of five genome-wide association studies of femoral neck and lumbar spine BMD in 19,195 subjects of Northern European descent. We identified 20 loci reaching genome-wide significance (GWS; P<5×10−8), of which 13 map to new regions including 1p31.3 (GPR177), 2p21 (SPTBN1), 3p22 (CTNNB1), 4q21.1 (MEPE), 5q14 (MEF2C), 7p14 (STARD3NL), 7q21.3 (FLJ42280), 11p11.2 (LRP4; ARHGAP1; F2), 11p14.1 (DCDC5), 11p15 (SOX6), 16q24 (FOXL1), 17q21 (HDAC5) and 17q12 (CRHR1). The metaanalysis also confirmed at GWS level, seven known BMD loci on 1p36 (ZBTB40), 6q25 (ESR1), 8q24 (TNFRSF11B), 11q13.4 (LRP5), 12q13 (SP7), 13q14 (TNFSF11), and 18q21 (TNFRSF11A). The numerous SNPs associated with BMD map to genes in signaling pathways with relevance to bone metabolism, and highlight the complex genetic architecture underlying osteoporosis and BMD variation.
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影响因子：
64.8
作者：
Frazer, Kelly A.;Ballinger, Dennis G.;Cox, David R.;Hinds, David A.;Stuve, Laura L.;Gibbs, Richard A.;Belmont, John W.;Boudreau, Andrew;Hardenbol, Paul;Leal, Suzanne M.;Pasternak, Shiran;Wheeler, David A.;Willis, Thomas D.;Yu, Fuli;Yang, Huanming;Zeng, Changqing;Gao, Yang;Hu, Haoran;Hu, Weitao;Li, Chaohua;Lin, Wei;Liu, Siqi;Pan, Hao;Tang, Xiaoli;Wang, Jian;Wang, Wei;Yu, Jun;Zhang, Bo;Zhang, Qingrun;Zhao, Hongbin;Zhao, Hui;Zhou, Jun;Gabriel, Stacey B.;Barry, Rachel;Blumenstiel, Brendan;Camargo, Amy;Defelice, Matthew;Faggart, Maura;Goyette, Mary;Gupta, Supriya;Moore, Jamie;Nguyen, Huy;Onofrio, Robert C.;Parkin, Melissa;Roy, Jessica;Stahl, Erich;Winchester, Ellen;Ziaugra, Liuda;Altshuler, David;Shen, Yan;Yao, Zhijian;Huang, Wei;Chu, Xun;He, Yungang;Jin, Li;Liu, Yangfan;Shen, Yayun;Sun, Weiwei;Wang, Haifeng;Wang, Yi;Wang, Ying;Xiong, Xiaoyan;Xu, Liang;Waye, Mary M. Y.;Tsui, Stephen K. W.;Wong, J. Tze-Fei;Galver, Luana M.;Fan, Jian-Bing;Gunderson, Kevin;Murray, Sarah S.;Oliphant, Arnold R.;Chee, Mark S.;Montpetit, Alexandre;Chagnon, Fanny;Ferretti, Vincent;Leboeuf, Martin;Olivier, Jean-Franccois;Phillips, Michael S.;Roumy, Stephanie;Sallee, Clementine;Verner, Andrei;Hudson, Thomas J.;Kwok, Pui-Yan;Cai, Dongmei;Koboldt, Daniel C.;Miller, Raymond D.;Pawlikowska, Ludmila;Taillon-Miller, Patricia;Xiao, Ming;Tsui, Lap-Chee;Mak, William;Song, You Qiang;Tam, Paul K. H.;Nakamura, Yusuke;Kawaguchi, Takahisa;Kitamoto, Takuya;Morizono, Takashi;Nagashima, Atsushi;Ohnishi, Yozo;Sekine, Akihiro;Tanaka, Toshihiro;Tsunoda, Tatsuhiko;Deloukas, Panos;Bird, Christine P.;Delgado, Marcos;Dermitzakis, Emmanouil T.;Gwilliam, Rhian;Hunt, Sarah;Morrison, Jonathan;Powell, Don;Stranger, Barbara E.;Whittaker, Pamela;Bentley, David R.;Daly, Mark J.;de Bakker, Paul I. W.;Barrett, Jeff;Chretien, Yves R.;Maller, Julian;McCarroll, Steve;Patterson, Nick;Pe'er, Itsik;Price, Alkes;Purcell, Shaun;Richter, Daniel J.;Sabeti, Pardis;Saxena, Richa;Schaffner, Stephen F.;Sham, Pak C.;Varilly, Patrick;Altshuler, David;Stein, Lincoln D.;Krishnan, Lalitha;Smith, Albert Vernon;Tello-Ruiz, Marcela K.;Thorisson, Gudmundur A.;Chakravarti, Aravinda;Chen, Peter E.;Cutler, David J.;Kashuk, Carl S.;Lin, Shin;Abecasis, Goncalo R.;Guan, Weihua;Li, Yun;Munro, Heather M.;Qin, Zhaohui Steve;Thomas, Daryl J.;McVean, Gilean;Auton, Adam;Bottolo, Leonardo;Cardin, Niall;Eyheramendy, Susana;Freeman, Colin;Marchini, Jonathan;Myers, Simon;Spencer, Chris;Stephens, Matthew;Donnelly, Peter;Cardon, Lon R.;Clarke, Geraldine;Evans, David M.;Morris, Andrew P.;Weir, Bruce S.;Tsunoda, Tatsuhiko;Johnson, Todd A.;Mullikin, James C.;Sherry, Stephen T.;Feolo, Michael;Skol, Andrew
通讯作者：
Skol, Andrew
影响因子：
3.5
作者：
de Bakker, Paul I. W.;Ferreira, Manuel A. R.;Voight, Benjamin F.
通讯作者：
Voight, Benjamin F.
影响因子：
30.8
作者：
Abecasis, GR;Cherny, SS;Cardon, LR
通讯作者：
Cardon, LR
影响因子：
4.6
作者：
Grundberg, Elin;Brandstrom, Helena;Pastinen, Tomi
通讯作者：
Pastinen, Tomi
影响因子：
30.8
作者：
Cho, Yoon Shin;Go, Min Jin;Kim, Hyung-Lae
通讯作者：
Kim, Hyung-Lae