Genome partitioning of genetic variation for height from 11,214 sibling pairs
Genome partitioning of genetic variation for height from 11,214 sibling pairs
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DOI：
10.1086/522934
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发表时间：
2007-11-01
影响因子：
9.8
通讯作者：
Martin, Nicholas G.
中科院分区：
文献类型：
--
作者：
Visscher, Peter M.;Macgregor, Stuart;Martin, Nicholas G.
一个多世纪以来，身高一直被用作理解人类定量遗传变异的模型。我们报告，整个基因组似乎有助于其加性遗传变异。我们使用来自三个国家的11,214对兄弟姐妹的基因型和表型来划分整个基因组的加性遗传变异。通过基因组扫描来估计来自兄弟姐妹的每条染色体的基因组在血统上相同的比例，我们估计了22条常染色体和X染色体中的每一条对身高的遗传能力。我们表明，累加性遗传变异分布在多条染色体上，并且至少有6条染色体（即3、4、8、15、17和18）对观察到的变异负责。事实上，这些数据与性状位点在整个基因组中的均匀分布并不矛盾。我们对一条染色体解释的方差的估计与该染色体与身高有暗示或显著联系的报道次数相关。由显性引起的方差不显著，但难以评估，因为加性成分和显性成分之间的抽样相关性很高。结果与没有任何大的染色体间上位效应一致。尽管提出的复杂性状结构涉及广泛的基因-基因和基因-环境相互作用，但我们的研究结果表明，人类身高的变化可以通过分布在所有常染色体上的许多位点来解释，这些位点具有基因作用的加性模式。
Height has been used for more than a century as a model by which to understand quantitative genetic variation in humans. We report that the entire genome appears to contribute to its additive genetic variance. We used genotypes and phenotypes of 11,214 sibling pairs from three countries to partition additive genetic variance across the genome. Using genome scans to estimate the proportion of the genomes of each chromosome from siblings that were identical by descent, we estimated the heritability of height contributed by each of the 22 autosomes and the X chromosome. We show that additive genetic variance is spread across multiple chromosomes and that at least six chromosomes (i. e., 3, 4, 8, 15, 17, and 18) are responsible for the observed variation. Indeed, the data are not inconsistent with a uniform spread of trait loci throughout the genome. Our estimate of the variance explained by a chromosome is correlated with the number of times suggestive or significant linkage with height has been reported for that chromosome. Variance due to dominance was not significant but was difficult to assess because of the high sampling correlation between additive and dominance components. Results were consistent with the absence of any large between-chromosome epistatic effects. Notwithstanding the proposed architecture of complex traits that involves widespread gene-gene and gene-environment interactions, our results suggest that variation in height in humans can be explained by many loci distributed over all autosomes, with an additive mode of gene action.