A genome-wide association study of northwestern Europeans involves the C-type natriuretic peptide signaling pathway in the etiology of human height variation.
A genome-wide association study of northwestern Europeans involves the C-type natriuretic peptide signaling pathway in the etiology of human height variation.
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DOI：
10.1093/hmg/ddp296
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发表时间：
2009-09-15
影响因子：
3.5
通讯作者：
Kayser M
中科院分区：
文献类型：
--
作者：
Estrada K;Krawczak M;Schreiber S;van Duijn K;Stolk L;van Meurs JB;Liu F;Penninx BW;Smit JH;Vogelzangs N;Hottenga JJ;Willemsen G;de Geus EJ;Lorentzon M;von Eller-Eberstein H;Lips P;Schoor N;Pop V;de Keijzer J;Hofman A;Aulchenko YS;Oostra BA;Ohlsson C;Boomsma DI;Uitterlinden AG;van Duijn CM;Rivadeneira F;Kayser M
西北欧人是世界上最高的人群之一。这些人的身高增长似乎已经达到了一个平台期，这表明普遍存在一个最佳环境，在这个环境中，遗传因素可能对人类的生长产生了特别强烈的影响。因此，我们对来自三个荷兰和一个德国人群的10074个人进行了一项身高全基因组关联研究（GWAS），使用220万个标记。通过基因分型，在另外6912个荷兰和瑞典血统的个体中发现了来自该GWAS的12个最显著的身高相关单核苷酸多态性（snp），染色体2q37.1上的遗传变异（rs6717918）在全基因组显著水平上与身高相关（p组合= 3.4 × 10−9）。值得注意的是，第二个SNP （rs6718438）位于距离rs6717918约450 bp的强LD中（r2 = 0.77），先前发现与29820名主要是西北欧血统的个体的身高有关，而附近的利钠肽前体C型（NPPC）基因的过度表达与过度生长和骨骼异常有关。我们还发现了一个位于5p14上的SNP (rs10472828)，该SNP位于利钠肽受体3 （NPR3）基因附近，编码NPPC配体的受体，与身高相关（Pcombined = 2.1 × 10−7）。综上所述，这些结果表明，涉及NPPC和NPR3基因的c型利钠肽信号通路的变异在决定人体身高方面起着重要作用。
Northwestern Europeans are among the tallest of human populations. The increase in body height in these people appears to have reached a plateau, suggesting the ubiquitous presence of an optimal environment in which genetic factors may have exerted a particularly strong influence on human growth. Therefore, we performed a genome-wide association study (GWAS) of body height using 2.2 million markers in 10 074 individuals from three Dutch and one German population-based cohorts. Upon genotyping, the 12 most significantly height-associated single nucleotide polymorphisms (SNPs) from this GWAS in 6912 additional individuals of Dutch and Swedish origin, a genetic variant (rs6717918) on chromosome 2q37.1 was found to be associated with height at a genome-wide significance level (Pcombined = 3.4 × 10−9). Notably, a second SNP (rs6718438) located ∼450 bp away and in strong LD (r2 = 0.77) with rs6717918 was previously found to be suggestive of a height association in 29 820 individuals of mainly northwestern European ancestry, and the over-expression of a nearby natriuretic peptide precursor type C (NPPC) gene, has been associated with overgrowth and skeletal anomalies. We also found a SNP (rs10472828) located on 5p14 near the natriuretic peptide receptor 3 (NPR3) gene, encoding a receptor of the NPPC ligand, to be associated with body height (Pcombined = 2.1 × 10−7). Taken together, these results suggest that variation in the C-type natriuretic peptide signaling pathway, involving the NPPC and NPR3 genes, plays an important role in determining human body height.
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作者：
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通讯作者：
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影响因子：
3.5
作者：
Lei, Shu-Feng;Tan, Li-Jun;Deng, Hong-Wen
通讯作者：
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影响因子：
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作者：
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de Bakker, Paul I. W.