Bivariate genome-wide association analyses of femoral neck bone geometry and appendicular lean mass.
Bivariate genome-wide association analyses of femoral neck bone geometry and appendicular lean mass.
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股骨颈骨几何形状和四肢瘦肉块的双变量全基因组关联分析
DOI：
10.1371/journal.pone.0027325
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Deng HW
中科院分区：
文献类型：
--
作者：
Sun L;Tan LJ;Lei SF;Chen XD;Li X;Pan R;Yin F;Liu QW;Yan XF;Papasian CJ;Deng HW
目的股骨颈几何参数（FNGP），如骨膜直径（W）、横截面积（CSA）、皮质厚度（CT）、屈曲比（BR）和截面模量（Z），与体瘦体重高度遗传相关。然而，这些表型共有的特定SNP/基因在很大程度上是未知的。方法为了确定FNGPs和非典型瘦体重（ALM）之间共享的特异性SNP/基因，我们在1，627名无关的中国汉族成年人（802名男性和825名女性）中扫描了690，000个SNP，并在2，286名无关的美国高加索人中进行了随访重复研究。结果我们鉴定了13个可能对FNGP和ALM都很重要的有趣SNPs。两个SNP，位于HK 2（己糖激酶2）基因的rs681900和UMOD（尿调蛋白）基因的rs 11859916，与FNGP和ALM呈双变量相关（分别为p= 7.58×10−6 ALM-BR和p =2.93×10−6 ALM-W）。 然后在高加索人中复制了这种关联，rs681900的相应p值为0.024，rs 11859916的相应p值为0.047。荟萃分析得出rs681900和rs 11859916的合并p值分别为3.05×10−6和2.31×10−6。我们的研究结果与先前的生物学研究一致，这些研究涉及FNGP和ALM中的HK 2和UMOD。我们的研究还确定了一组11个连续的SNP，它们跨越130 kb的区域，与FNGP和ALM双变量相关，ALM-BR的p值范围为3.06×10−7至4.60×10−6。该区域包含两个相邻的miRNA编码基因，MIR 873（MicroRNA 873）和MIR 876（MicroRNA 876）。结论HK 2、UMOD、MIR 873和MIR 876是FNGPs和ALM的多效基因，在FNGPs和ALM的共同调控中发挥重要作用。
Objective Femoral neck geometric parameters (FNGPs), such as periosteal diameter (W), cross-sectional area (CSA), cortical thickness (CT), buckling ratio (BR), and section modulus (Z), are highly genetically correlated with body lean mass. However, the specific SNPs/genes shared by these phenotypes are largely unknown. Methods To identify the specific SNPs/genes shared between FNGPs and appendicular lean mass (ALM), we performed an initial bivariate genome-wide association study (GWAS) by scanning ∼690,000 SNPs in 1,627 unrelated Han Chinese adults (802 males and 825 females) and a follow-up replicate study in 2,286 unrelated US Caucasians. Results We identified 13 interesting SNPs that may be important for both FNGPs and ALM. Two SNPs, rs681900 located in the HK2 (hexokinase 2) gene and rs11859916 in the UMOD (uromodulin) gene, were bivariately associated with FNGPs and ALM (p = 7.58×10−6 for ALM-BR and p = 2.93×10−6 for ALM-W, respectively). The associations were then replicated in Caucasians, with corresponding p values of 0.024 for rs681900 and 0.047 for rs11859916. Meta-analyses yielded combined p values of 3.05×10−6 and 2.31×10−6 for rs681900 and rs11859916, respectively. Our findings are consistent with previous biological studies that implicated HK2 and UMOD in both FNGPs and ALM. Our study also identified a group of 11 contiguous SNPs, which spanned a region of ∼130 kb, were bivariately associated with FNGPs and ALM, with p values ranging from 3.06×10−7 to 4.60×10−6 for ALM-BR. The region contained two neighboring miRNA coding genes, MIR873 (MicroRNA873) and MIR876 (MicroRNA876). Conclusion Our study implicated HK2, UMOD, MIR873 and MIR876, as pleiotropic genes underlying variation of both FNGPs and ALM, thus suggesting their important functional roles in co-regulating both FNGPs and ALM.
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DOI：
10.1177/1466424007079491
发表时间：
2007-07-01
期刊：
JOURNAL OF THE ROYAL SOCIETY FOR THE PROMOTION OF HEALTH
影响因子：
--
作者：
Handoll, Helen Hanora Georgina;Gillespie, William John;Madhok, Rajan
通讯作者：
Madhok, Rajan
影响因子：
5.5
作者：
Marcora, S.;Casanova, F.;Lemmey, A.
通讯作者：
Lemmey, A.
影响因子：
3.3
作者：
Howell, Gareth R.;Shindo, Mami;Schimenti, John C.
通讯作者：
Schimenti, John C.
影响因子：
6.2
作者：
Beck, TJ;Oreskovic, TL;Cummings, SR
通讯作者：
Cummings, SR
影响因子：
4
作者：
Crabtree, NJ;Kroger, H;Reeve, J
通讯作者：
Reeve, J