Rivadeneira Fernando, Styrkársdottir Unnur, Estrada Karol, Halldórsson 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 André G
Department of Internal Medicine, Rotterdam, The Netherlands.
Nat Genet. 2009 Nov;41(11):1199-206. doi: 10.1038/ng.446. Epub 2009 Oct 4.
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 BMD loci that reached genome-wide significance (GWS; P < 5 x 10(-8)), of which 13 map to regions not previously associated with this trait: 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 meta-analysis 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 many SNPs associated with BMD map to genes in signaling pathways with relevance to bone metabolism and highlight the complex genetic architecture that underlies osteoporosis and variation in BMD.
骨矿物质密度（BMD）是一种可遗传的复杂性状，用于骨质疏松症的临床诊断和骨折风险评估。我们对19195名北欧血统受试者的五项股骨颈和腰椎BMD全基因组关联研究进行了荟萃分析。我们确定了20个达到全基因组显著性（GWS；P < 5×10⁻⁸）的BMD位点，其中13个定位于以前未与该性状相关的区域：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）和17q12（CRHR1）。荟萃分析还在GWS水平上证实了1p36（ZBTB40）、6q25（ESR1）、8q24（TNFRSF11B）、11q13.4（LRP5）、12q13（SP7）、13q14（TNFSF11）和18q21（TNFRSF11A）上的七个已知BMD位点。许多与BMD相关的单核苷酸多态性定位于与骨代谢相关的信号通路中的基因，突出了骨质疏松症和BMD变异背后复杂的遗传结构。
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