Common variants in the region around Osterix are associated with bone mineral density and growth in childhood.
Common variants in the region around Osterix are associated with bone mineral density and growth in childhood.
复制标题
Osterix周围地区的常见变体与骨矿物质密度和儿童期生长有关。
DOI：
10.1093/hmg/ddp052
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发表时间：
2009-04-15
影响因子：
3.5
通讯作者：
Evans DM
中科院分区：
文献类型：
--
作者：
Timpson NJ;Tobias JH;Richards JB;Soranzo N;Duncan EL;Sims AM;Whittaker P;Kumanduri V;Zhai G;Glaser B;Eisman J;Jones G;Nicholson G;Prince R;Seeman E;Spector TD;Brown MA;Peltonen L;Smith GD;Deloukas P;Evans DM
青春期达到的峰值骨量是以后生活中骨量的决定因素。为了确定影响骨密度（BMD）的遗传变异，我们对雅芳父母和儿童纵向研究（ALSPAC）的1518名儿童进行了BMD和相关性状的全基因组关联研究。我们将结果与134名高或低髋部BMD的成人的扫描结果进行了比较。我们确定了12号染色体上含有Osterix（SP 7）基因座的区域与BMD的相关性，Osterix（SP 7）基因座是一种负责调节成骨细胞分化的转录因子（ALSPAC：P = 5.8 × 10−4;澳大利亚：P = 3.7 × 10−4）。该区域先前已显示出与冰岛人群中成人髋关节和腰椎BMD相关的证据，以及英国人群中的名义相关性。对这些现有研究的荟萃分析显示，Osterix区域的SNP与成人腰椎BMD之间存在强相关性（P = 9.9 × 10−11）。鉴于这些发现，我们对来自ALSPAC的另外3692名患有全身BMD的个体进行了基因分型，并证实了儿童中的相关性（P = 5.4 × 10 - 5）。此外，所有SNPs与ALSPAC儿童的身高相关，但与体重或体重指数无关，当身高作为协变量纳入回归方程时，与全身BMD的相关性减弱。我们的结论是，在该地区的Osterix的遗传变异与BMD在儿童和成人可能通过对生长的主要影响。
Peak bone mass achieved in adolescence is a determinant of bone mass in later life. In order to identify genetic variants affecting bone mineral density (BMD), we performed a genome-wide association study of BMD and related traits in 1518 children from the Avon Longitudinal Study of Parents and Children (ALSPAC). We compared results with a scan of 134 adults with high or low hip BMD. We identified associations with BMD in an area of chromosome 12 containing the Osterix (SP7) locus, a transcription factor responsible for regulating osteoblast differentiation (ALSPAC: P = 5.8 × 10−4; Australia: P = 3.7 × 10−4). This region has previously shown evidence of association with adult hip and lumbar spine BMD in an Icelandic population, as well as nominal association in a UK population. A meta-analysis of these existing studies revealed strong association between SNPs in the Osterix region and adult lumbar spine BMD (P = 9.9 × 10−11). In light of these findings, we genotyped a further 3692 individuals from ALSPAC who had whole body BMD and confirmed the association in children as well (P = 5.4 × 10−5). Moreover, all SNPs were related to height in ALSPAC children, but not weight or body mass index, and when height was included as a covariate in the regression equation, the association with total body BMD was attenuated. We conclude that genetic variants in the region of Osterix are associated with BMD in children and adults probably through primary effects on growth.
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影响因子：
30.8
作者：
Styrkarsdottir, Unnur;Halldorsson, Bjarni V.;Stefansson, Kari
通讯作者：
Stefansson, Kari
影响因子：
64.5
作者：
Nakashima, K;Zhou, X;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
影响因子：
5.8
作者：
Chevalley, Thierry;Bonjour, Jean-Philippe;Rizzoli, Rene
通讯作者：
Rizzoli, Rene
影响因子：
4.2
作者：
Koay, M. Audrey;Tobias, Jonathan H.;Brown, Matthew A.
通讯作者：
Brown, Matthew A.
影响因子：
6.2
作者：
McGuigan, FEA;Murray, L;Ralston, SH
通讯作者：
Ralston, SH