Genetic linkage of human height is confirmed to 9q22 and Xq24
Genetic linkage of human height is confirmed to 9q22 and Xq24
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DOI：
10.1007/s00439-006-0136-y
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发表时间：
2006-04-01
期刊：
影响因子：
5.3
通讯作者：
Deng, HW
中科院分区：
文献类型：
--
作者：
Liu, YZ;Xiao, P;Deng, HW
人类的身高是一个重要的和可遗传的特征。我们之前的两项全基因组连锁研究使用了630（WG研究）和1，816名高加索人的扩展样本（WG 2研究），确定了9q22 [WG 2研究中的最大LOD得分（MLS）= 2.74]，并初步确认了Xq24（WG 1研究中的两点LOD得分= 1.91，WG 2研究中的2.64）与身高相关。在这里，我们进一步扩展了包含3，726名高加索人的大样本，进行了新的全基因组连锁扫描，并高度显著地证实了这两个区域与身高的连锁。在9q22上检测到的MLS为4.34，Xq24的两点LOD评分为5.63。在独立子样本中（即，未参与WG 1和WG 2研究的受试者），这两个区域也获得了显著的经验P值（分别为0.002和0.004），用于“区域方面”的连锁确认。重要的是，这两个区域是在不同于WG 1和WG 2研究的基因分型平台上复制的（即，不同的标记物组和不同的基因分型仪器）。有趣的是，9 q22含有生长板发育所需的ROR 2基因，而Xq 24与身材矮小有关。在复杂性状的连锁研究领域，我们的研究是来自同一种族的单一人群的最大样本，我们目前的研究以及之前的两项研究提供了压倒性的证据，证实了9q22和Xq24的身高变异。特别是，我们的三个连续的全基因组研究是独特的价值，因为它们代表了第一个实际的（而不是模拟）的例子，如何显着增加样本量可能会提高人类复杂性状的连锁检测。
Human height is an important and heritable trait. Our previous two genome-wide linkage studies using 630 (WG study) and an extended sample of 1,816 Caucasians (WG2 study) identified 9q22 [maximum LOD score (MLS) = 2.74 in the WG2 study] and preliminarily confirmed Xq24 (two-point LOD score= 1.91 in the WG1 study, 2.64 in the WG2 study) linked to height. Here, with a much further extended large sample containing 3,726 Caucasians, we performed a new genome-wide linkage scan and confirmed, in high significance, the two regions' linkage to height. An MLS of 4.34 was detected on 9q22 and a two-point LOD score of 5.63 was attained for Xq24. In an independent subsample (i.e., the subjects not involved in the WG 1 and WG2 studies), the two regions also achieved significant empirical P values (0.002 and 0.004, respectively) for "region-wise" linkage confirmation. Importantly, the two regions were replicated on a genotyping platform different from the WG1 and WG2 studies (i.e., a different set of markers and different genotyping instruments). Interestingly, 9q22 harbors the ROR2 gene, which is required for growth plate development, and Xq24 was linked to short stature. With the largest sample from a single population of the same ethnicity in the field of linkage studies for complex traits, our current study, together with two previous ones, provided overwhelming evidence substantiating 9q22 and Xq24 for height variation. In particular, our three consecutive whole genome studies are uniquely valuable as they represent the first practical (rather than simulated) example of how significant increase in sample size may improve linkage detection for human complex traits.