Identification of ten loci associated with height highlights new biological pathways in human growth.
Identification of ten loci associated with height highlights new biological pathways in human growth.
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DOI：
10.1038/ng.125
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发表时间：
2008-05
期刊：
影响因子：
30.8
通讯作者：
Hirschhorn, Joel N.
中科院分区：
文献类型：
--
作者：
Lettre, Guillaume;Jackson, Anne U.;Gieger, Christian;Schumacher, Fredrick R.;Berndt, Sonja I.;Sanna, Serena;Eyheramendy, Susana;Voight, Benjamin F.;Butler, Johannah L.;Guiducci, Candace;Illig, Thomas;Hackett, Rachel;Heid, Iris M.;Jacobs, Kevin B.;Lyssenko, Valeriya;Uda, Manuela;Boehnke, Michael;Chanock, Stephen J.;Groop, Leif C.;Hu, Frank B.;Isomaa, Bo;Kraft, Peter;Peltonen, Leena;Salomaa, Veikko;Schlessinger, David;Hunter, David J.;Hayes, Richard B.;Abecasis, Goncalo R.;Wichmann, H-Erich;Mohlke, Karen L.;Hirschhorn, Joel N.
身高是一个典型的多基因性状，反映了多个尚未发现的遗传因素的综合影响。我们对来自15，821名个体的220万个SNP的身高全基因组关联研究数据进行了荟萃分析，并在> 10，000名受试者中随访了最强的发现。10个新发现的位点和2个先前报道的位点与身高变异密切相关（P值从4 × 10-7到8 × 10-22）。这12个基因座加在一起占身高群体变异的2%。具有≤8个身高增加等位基因和≥16个身高增加等位基因的个体在身高上相差约3.5 cm。新鉴定的基因座，沿着几个具有强烈暗示性关联的额外基因座，包括强生物学候选基因和意外基因，并突出几个途径（let-7靶点、染色质重塑蛋白和Hedgehog信号传导）作为人类身高的重要调节因子。这些结果扩展了人类身高的生物学调节和这一经典复杂性状的遗传结构的图景。
Height is a classic polygenic trait, reflecting the combined influence of multiple as-yet-undiscovered genetic factors. We carried out a meta-analysis of genome-wide association study data of height from 15,821 individuals at 2.2 million SNPs, and followed up the strongest findings in >10,000 subjects. Ten newly identified and two previously reported loci were strongly associated with variation in height (P values from 4 × 10-7 to 8 × 10-22). Together, these 12 loci account for ~2% of the population variation in height. Individuals with ≤8 height-increasing alleles and ≥16 height-increasing alleles differ in height by ~3.5 cm. The newly identified loci, along with several additional loci with strongly suggestive associations, encompass both strong biological candidates and unexpected genes, and highlight several pathways (let-7 targets, chromatin remodeling proteins and Hedgehog signaling) as important regulators of human stature. These results expand the picture of the biological regulation of human height and of the genetic architecture of this classical complex trait.
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