Montreal Heart Institute, Montréal, Canada.
PLoS Genet. 2011 Oct;7(10):e1002298. doi: 10.1371/journal.pgen.1002298. Epub 2011 Oct 6.
Adult height is a classic polygenic trait of high heritability (h(2) approximately 0.8). More than 180 single nucleotide polymorphisms (SNPs), identified mostly in populations of European descent, are associated with height. These variants convey modest effects and explain approximately10% of the variance in height. Discovery efforts in other populations, while limited, have revealed loci for height not previously implicated in individuals of European ancestry. Here, we performed a meta-analysis of genome-wide association (GWA) results for adult height in 20,427 individuals of African ancestry with replication in up to 16,436 African Americans. We found two novel height loci (Xp22-rs12393627, P = 3.4×10(-12) and 2p14-rs4315565, P = 1.2×10(-8)). As a group, height associations discovered in European-ancestry samples replicate in individuals of African ancestry (P = 1.7×10(-4) for overall replication). Fine-mapping of the European height loci in African-ancestry individuals showed an enrichment of SNPs that are associated with expression of nearby genes when compared to the index European height SNPs (P<0.01). Our results highlight the utility of genetic studies in non-European populations to understand the etiology of complex human diseases and traits.
成人身高是一种经典的高度遗传多基因特征（h²约为 0.8）。大多数在欧洲血统人群中发现的超过 180 个单核苷酸多态性（SNP）与身高相关。这些变体具有适度的影响，可解释身高变异的约 10%。尽管其他人群的发现工作有限，但已经揭示了以前与欧洲血统个体无关的身高基因座。在这里，我们对非洲血统的 20,427 名个体进行了全基因组关联（GWA）分析，结果显示成年身高与两个新的身高基因座（Xp22-rs12393627，P=3.4×10⁻¹²和 2p14-rs4315565，P=1.2×10⁻⁸）相关。作为一个群体，在欧洲血统样本中发现的身高关联在非洲血统个体中得到了复制（总体复制的 P=1.7×10⁻⁴）。在非洲血统个体中对欧洲身高基因座进行精细映射显示，与索引欧洲身高 SNP 相比，与附近基因表达相关的 SNP 更为丰富（P<0.01）。我们的研究结果强调了在非欧洲人群中进行遗传研究以了解复杂人类疾病和特征的病因学的重要性。
