A genome-wide linkage scan for bone mineral density in an extended sample: evidence for linkage on 11q23 and Xq27
A genome-wide linkage scan for bone mineral density in an extended sample: evidence for linkage on 11q23 and Xq27
复制标题
DOI：
10.1136/jmg.2004.020396
复制
发表时间：
2004-10-01
影响因子：
4
通讯作者：
Deng, HW
中科院分区：
文献类型：
--
作者：
Shen, H;Zhang, YY;Deng, HW
背景：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。大多数 BMD 变异是由遗传效应决定的。此前曾报道过对 53 个白人谱系的 630 名受试者进行了试点全基因组连锁扫描 (WGS)。多个基因组区域被认为与 BMD 变异有关。目的：证实这些先前的发现并检测新的基因组区域。方法：对扩展样本进行全基因组测序，样本大小几乎增加了两倍（来自 79 个谱系的 1816 名受试者）。所有受试者均使用人类基因组中 451 个微卫星标记进行基因分型，这些微卫星标记的间距约为 8.1 cM。采用方差分量法进行两点和多点连锁分析。结果：在Xq27上获得最强的连锁信号，腕部BMD的两点LOD得分为4.30，髋部BMD的两点LOD得分分别为2.57。另一个重要区域是 11q23，在多点分析中，该区域的脊柱 BMD 最高 LOD 得分为 3.13，证实了两项早期独立研究中该区域的结果。在 7p14 和 20p12 上也发现了暗示性的连锁证据。结论：结合其他研究的结果，当前的研究进一步描述了骨量的遗传基础，并强调了增加样本量以确认连锁发现和识别新的连锁区域的重要性。
Background: 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.Objective: To substantiate these previous findings and detect new genomic regions.Methods: 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 similar to8.1 cM apart across the human genome. Two point and multipoint linkage analyses were carried out using the variance component method.Results: 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.Conclusions: 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.