全基因组关联研究中鉴定的与身高相关的基因座在儿童身高决定中的作用。

The role of height-associated loci identified in genome wide association studies in the determination of pediatric stature.

机构信息

Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.

出版信息

BMC Med Genet. 2010 Jun 14;11:96. doi: 10.1186/1471-2350-11-96.

Abstract

BACKGROUND

Human height is considered highly heritable and correlated with certain disorders, such as type 2 diabetes and cancer. Despite environmental influences, genetic factors are known to play an important role in stature determination. A number of genetic determinants of adult height have already been established through genome wide association studies.

METHODS

To examine 51 single nucleotide polymorphisms (SNPs) corresponding to the 46 previously reported genomic loci for height in 8,184 European American children with height measurements. We leveraged genotyping data from our ongoing GWA study of height variation in children in order to query the 51 SNPs in this pediatric cohort.

RESULTS

Sixteen of these SNPs yielded at least nominally significant association to height, representing fifteen different loci including EFEMP1-PNPT1, GPR126, C6orf173, SPAG17, Histone class 1, HLA class III and GDF5-UQCC. Other loci revealed no evidence for association, including HMGA1 and HMGA2. For the 16 associated variants, the genotype score explained 1.64% of the total variation for height z-score.

CONCLUSION

Among 46 loci that have been reported to associate with adult height to date, at least 15 also contribute to the determination of height in childhood.

摘要

背景

人类身高被认为具有高度遗传性,并与某些疾病相关,如 2 型糖尿病和癌症。尽管受到环境影响,但遗传因素在身高决定中起着重要作用。通过全基因组关联研究,已经确定了许多成人身高的遗传决定因素。

方法

在 8184 名欧洲裔美国儿童中,我们检查了与之前报道的 46 个身高相关基因组座相对应的 51 个单核苷酸多态性(SNP),这些儿童的身高均有测量。我们利用正在进行的儿童身高变异全基因组关联研究中的基因分型数据,来查询该儿科队列中的 51 个 SNP。

结果

其中 16 个 SNP 与身高至少具有名义上的显著关联,代表了 15 个不同的基因座,包括 EFEMP1-PNPT1、GPR126、C6orf173、SPAG17、Histone class 1、HLA class III 和 GDF5-UQCC。其他基因座没有显示出与身高相关的证据,包括 HMGA1 和 HMGA2。对于 16 个关联的变体,基因型评分解释了身高 z 分数总变异的 1.64%。

结论

在迄今为止与成人身高相关的 46 个基因座中,至少有 15 个也有助于儿童身高的决定。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5fb/2894790/d6ef8d4c1b79/1471-2350-11-96-1.jpg

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