Shen Hui, Long Ji-Rong, Xiong Dong-Hai, Liu Yong-Jun, Liu Yao-Zhong, Xiao Peng, Zhao Lan-Juan, Dvornyk Volodymyr, Zhang Yuan-Yuan, Rocha-Sanchez Sonia, Liu Peng-Yuan, Li Jin-Long, Deng Hong-Wen
Osteoporosis Research Center, Creighton University, Omaha, Nebraska 68131, USA.
J Bone Miner Res. 2005 Nov;20(11):1973-82. doi: 10.1359/JBMR.050715. Epub 2005 Jul 18.
A genome-wide linkage scan was performed in a sample of 79 multiplex pedigrees to identify genomic regions linked to femoral neck cross-sectional geometry. Potential quantitative trait loci were detected at several genomic regions, such as 10q26, 20p12-q12, and chromosome X.
Bone geometry is an important determinant of bone strength and osteoporotic fractures. Previous studies have shown that femoral neck cross-sectional geometric variables are under genetic controls. To identify genetic loci underlying variation in femoral neck cross-sectional geometry, we conducted a whole genome linkage scan for four femoral neck cross-sectional geometric variables in 79 multiplex white pedigrees.
A total of 1816 subjects from 79 pedigrees were genotyped with 451 microsatellite markers across the human genome. We performed linkage analyses on the entire data, as well as on men and women separately.
Significant linkage evidence was identified at 10q26 for buckling ratio (LOD = 3.27) and Xp11 (LOD = 3.45) for cortical thickness. Chromosome region 20p12-q12 showed suggestive linkage with cross-sectional area (LOD = 2.33), cortical thickness (LOD = 2.09), and buckling ratio (LOD = 1.94). Sex-specific linkage analyses further supported the importance of 20p12-q12 for cortical thickness (LOD = 2.74 in females and LOD = 1.88 in males) and buckling ratio (LOD = 5.00 in females and LOD = 3.18 in males).
This study is the first genome-wide linkage scan searching for quantitative trait loci underlying femoral neck cross-sectional geometry in humans. The identification of the genes responsible for bone geometric variation will improve our knowledge of bone strength and aid in development of diagnostic approaches and interventions for osteoporotic fractures.
对79个多重家系样本进行全基因组连锁扫描，以确定与股骨颈横截面几何形状相关的基因组区域。在几个基因组区域检测到潜在的数量性状基因座，如10q26、20p12 - q12和X染色体。
骨几何形状是骨强度和骨质疏松性骨折的重要决定因素。先前的研究表明，股骨颈横截面几何变量受遗传控制。为了确定股骨颈横截面几何形状变异的遗传位点，我们对79个多重白人家庭的四个股骨颈横截面几何变量进行了全基因组连锁扫描。
对来自79个家系的1816名受试者进行全基因组451个微卫星标记的基因分型。我们对整个数据以及分别对男性和女性进行了连锁分析。
在10q26处发现屈曲比有显著连锁证据（LOD = 3.27），在Xp11处发现皮质厚度有显著连锁证据（LOD = 3.45）。染色体区域20p12 - q12显示与横截面积（LOD = 2.33）、皮质厚度（LOD = 2.09）和屈曲比（LOD = 1.94）有提示性连锁。性别特异性连锁分析进一步支持了20p12 - q12对皮质厚度（女性LOD = 2.74，男性LOD = 1.88）和屈曲比（女性LOD = 5.00，男性LOD = 3.18）的重要性。
本研究是首次在人类中进行全基因组连锁扫描以寻找股骨颈横截面几何形状的数量性状基因座。确定负责骨几何形状变异的基因将提高我们对骨强度的认识，并有助于开发骨质疏松性骨折的诊断方法和干预措施。
