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Nature genetics · 2012

Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.

СтатьяМетаанализПоддержка NIH: внешняя программаResearch Support, N.I.H., IntramuralПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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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 L S, 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 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, 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

Аннотация

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 × 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 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 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.

Предметные рубрики MeSH

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

Реквизиты и контакты