Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, College of Medicine, Xi'an Jiaotong University, Xi'an, PR China.
PLoS One. 2012;7(9):e44292. doi: 10.1371/journal.pone.0044292. Epub 2012 Sep 5.
Human height is a highly heritable trait considered as an important factor for health. There has been limited success in identifying the genetic factors underlying height variation. We aim to identify sequence variants associated with adult height by a genome-wide association study of copy number variants (CNVs) in Chinese.
Genome-wide CNV association analyses were conducted in 1,625 unrelated Chinese adults and sex specific subgroup for height variation, respectively. Height was measured with a stadiometer. Affymetrix SNP6.0 genotyping platform was used to identify copy number polymorphisms (CNPs). We constructed a genomic map containing 1,009 CNPs in Chinese individuals and performed a genome-wide association study of CNPs with height.
We detected 10 significant association signals for height (p<0.05) in the whole population, 9 and 11 association signals for Chinese female and male population, respectively. A copy number polymorphism (CNP12587, chr18:54081842-54086942, p = 2.41 × 10(-4)) was found to be significantly associated with height variation in Chinese females even after strict Bonferroni correction (p = 0.048). Confirmatory real time PCR experiments lent further support for CNV validation. Compared to female subjects with two copies of the CNP, carriers of three copies had an average of 8.1% decrease in height. An important candidate gene, ubiquitin-protein ligase NEDD4-like (NEDD4L), was detected at this region, which plays important roles in bone metabolism by binding to bone formation regulators.
Our findings suggest the important genetic variants underlying height variation in Chinese.
身高是一种高度遗传的特征，被认为是健康的重要因素。虽然已经在确定身高变异的遗传因素方面取得了有限的成功，但我们仍在努力寻找。我们旨在通过对中国成年人进行全基因组关联研究，发现与成年身高相关的序列变异。
分别对 1625 名无血缘关系的中国成年人和性别特异性亚组进行全基因组 CNV 关联分析，以分别研究身高的变异性。身高采用测高仪进行测量。使用 Affymetrix SNP6.0 基因分型平台识别拷贝数多态性（CNPs）。我们构建了一个包含 1009 个中国人 CNPs 的基因组图谱，并对 CNPs 与身高的全基因组关联进行了研究。
我们在全人群中检测到 10 个与身高相关的显著关联信号（p<0.05），在女性和男性人群中分别检测到 9 个和 11 个关联信号。发现一个拷贝数多态性（CNP12587，chr18:54081842-54086942，p = 2.41×10(-4)）与中国女性的身高变化显著相关，即使在严格的 Bonferroni 校正后（p = 0.048）也是如此。实时 PCR 实验进一步证实了 CNV 的验证。与携带两个 CNP 拷贝的女性相比，携带三个拷贝的女性身高平均降低了 8.1%。在该区域检测到一个重要的候选基因，泛素蛋白连接酶 NEDD4 样（NEDD4L），它通过与骨形成调节剂结合，在骨代谢中发挥重要作用。
我们的研究结果表明，中国人群身高变化的重要遗传变异。
