Shen H, Zhang Y-Y, Long J-R, Xu F-H, Liu Y-Z, Xiao P, Zhao L-J, Xiong D-H, Liu Y-J, Dvornyk V, Rocha-Sanchez S, Liu P-Y, Li J-L, Conway T, Davies K M, Recker R R, Deng H-W
Osteoporosis Research Center, Creighton University, Omaha, Nebraska 68131, USA.
J Med Genet. 2004 Oct;41(10):743-51. doi: 10.1136/jmg.2004.020396.
Osteoporosis is a major public health problem, mainly quantified by low bone mineral density (BMD). The majority of BMD variation is determined by genetic effects. A pilot whole genome linkage scan (WGS) was previously reported in 53 white pedigrees with 630 subjects. Several genomic regions were suggested to be linked to BMD variation.
To substantiate these previous findings and detect new genomic regions.
A WGS was conducted on an extended sample where the size was almost tripled (1816 subjects from 79 pedigrees). All the subjects were genotyped with 451 microsatellite markers spaced approximately 8.1 cM apart across the human genome. Two point and multipoint linkage analyses were carried out using the variance component method.
The strongest linkage signal was obtained on Xq27 with two point LOD scores of 4.30 for wrist BMD, and 2.57 for hip BMD, respectively. Another important region was 11q23, which achieved a maximum LOD score of 3.13 for spine BMD in multipoint analyses, confirming the results on this region in two earlier independent studies. Suggestive linkage evidence was also found on 7p14 and 20p12.
Together with the findings from other studies, the current study has further delineated the genetic basis of bone mass and highlights the importance of increasing sample size to confirm linkage findings and to identify new regions of linkage.
骨质疏松症是一个主要的公共卫生问题，主要通过低骨矿物质密度（BMD）来量化。BMD的大部分变异由遗传效应决定。先前有一项针对53个白人系谱中630名受试者的全基因组连锁扫描（WGS）试点研究报告。有几个基因组区域被认为与BMD变异有关。
证实先前的这些发现并检测新的基因组区域。
对一个扩大样本进行WGS，样本量几乎增加了两倍（来自79个系谱的1816名受试者）。所有受试者都用451个微卫星标记进行基因分型，这些标记在人类基因组中相隔约8.1厘摩。使用方差成分法进行两点和多点连锁分析。
在Xq27上获得了最强的连锁信号，手腕BMD的两点对数优势分数为4.30，髋部BMD的为2.57。另一个重要区域是11q23，在多点分析中脊柱BMD的最大对数优势分数为3.13，证实了两项早期独立研究中该区域的结果。在7p14和20p12上也发现了提示性连锁证据。
与其他研究结果一起，本研究进一步阐明了骨量的遗传基础，并强调了增加样本量以确认连锁发现和识别新连锁区域的重要性。
