Deng Fei-Yan, Xiao Peng, Lei Shu-Feng, Zhang Lei, Yang Fang, Tang Zi-Hui, Liu Peng-Yuan, Liu Yong-Jun, Recker Robert R, Deng Hong-Wen
Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
J Bone Miner Res. 2007 Jun;22(6):808-16. doi: 10.1359/jbmr.070303.
A genome-wide bivariate analysis was conducted for femoral neck GPs and TBLM in a large white sample. We found QTLs shared by GPs and TBLM in the total sample and the sex-specific samples. QTLs with potential pleiotropy were also disclosed.
Previous studies have suggested that femoral neck cross-section geometric parameters (FNCS-GPs), including periosteal diameter (W), cross-sectional area (CSA), cortical thickness (CT), buckling ratio (BR), and section modulus (Z), are genetically correlated with total body lean mass (TBLM). However, the shared genetic factors between them are unknown.
To identify the specific QTLs shared by FNCS-GPs and TBLM, we performed bivariate whole genome linkage analysis (WGLA) in a large sample of 451 white families made up of 4498 subjects.
Multipoint bivariate linkage analyses for 22 autosomes showed evidence of suggestive or significant linkages (thresholds of LOD = 2.3 and 3.7, respectively) to chromosomes 3q12 and 20q13 in the entire sample, 6p25 and 10q24 in women, and 4p15, 5q34-35 and 7q21 in men. Two-point linkage analyses for chromosome X showed strong linkage to Xp22.13, Xp11.4, Xq22.3, Xq23-24, and Xq25. Complete pleiotropy was identified on 10q24 and 5q35 for TBLM and BR in women and for TBLM and CT in men, respectively. Furthermore, chromosomes 5q34-35, 7q21, 10q24, 20q13, Xp22.13, Xp11.4, and Xq25 are also of importance because of their linkage to multiple trait pairs. For example, linkage to chromosome 10q24 was found for TBLM x W (LOD = 2.31), TBLM x CT (LOD = 2.51), TBLM x CSA (LOD = 2.51), TBLM x BR (LOD = 2.64), and TBLM x Z (LOD = 2.55) in women.
In this study, we identified several genomic regions (e.g., 3q12 and 20q13) that seem to be linked to both FNCS-GPs and TBLM. These regions are of interesting because they may harbor genes that may contribute to variation in both FNCS-GPs and TBLM.
在一个大型白人样本中对股骨颈几何参数（GPs）和全身瘦体重（TBLM）进行了全基因组双变量分析。我们在总样本和性别特异性样本中发现了GPs和TBLM共有的数量性状基因座（QTLs）。还揭示了具有潜在多效性的QTLs。
先前的研究表明，股骨颈横截面几何参数（FNCS - GPs），包括骨膜直径（W）、横截面积（CSA）、皮质厚度（CT）、屈曲比（BR）和截面模量（Z），与全身瘦体重（TBLM）存在遗传相关性。然而，它们之间共享的遗传因素尚不清楚。
为了确定FNCS - GPs和TBLM共有的特定QTLs，我们在一个由4498名受试者组成的451个白人家庭的大样本中进行了双变量全基因组连锁分析（WGLA）。
对22条常染色体的多点双变量连锁分析显示，在整个样本中，与3号染色体q12和20号染色体q13存在提示性或显著连锁（LOD阈值分别为2.3和3.7）；在女性中，与6号染色体p25和10号染色体q24存在连锁；在男性中，与4号染色体p15、5号染色体q34 - 35和7号染色体q21存在连锁。对X染色体的两点连锁分析显示，与Xp22.13、Xp11.4、Xq22.3、Xq23 - 24和Xq25存在强连锁。分别在女性的10号染色体q24和5号染色体q35以及男性的10号染色体q24和5号染色体q35上鉴定出TBLM与BR以及TBLM与CT的完全多效性。此外，5号染色体q34 - 3�、7号染色体q21、10号染色体q24、20号染色体q13、Xp22.13、Xp11.4和Xq25也很重要，因为它们与多个性状对存在连锁。例如，在女性中，发现10号染色体q24与TBLM×W（LOD = 2.31）、TBLM×CT（LOD = 2.51）、TBLM×CSA（LOD = 2.51）、TBLM×BR（LOD = 2.64）和TBLM×Z（LOD = 2.55）存在连锁。
在本研究中，我们鉴定出了几个似乎与FNCS - GPs和TBLM都相关的基因组区域（如3q12和20q13）。这些区域很有趣，因为它们可能包含对FNCS - GPs和TBLM的变异都有贡献的基因。
