Evidence of Inbreeding Depression on Human Height
Evidence of Inbreeding Depression on Human Height
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DOI：
10.1371/journal.pgen.1002655
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发表时间：
2012-07-01
期刊：
影响因子：
4.5
通讯作者：
Wilson, James F.
中科院分区：
文献类型：
--
作者：
McQuillan, Ruth;Eklund, Niina;Wilson, James F.
身高是一个典型的高度遗传的复杂性状，80%-90%的变异可由遗传因素解释。近年来，全基因组关联研究（GWAS）已经成功地确定了许多常见的影响人类身高的加性变异;然而，很少有人关注隐性遗传效应的潜在作用。在这里，我们通过分析来自21个不同人群样本的35，000多人的近亲繁殖抑制对成年身高的影响，研究了全基因组隐性效应。我们发现身高和全基因组纯合性之间存在高度显著的负相关，相当于与无关个体的后代相比，近亲后代的身高减少了3厘米，在控制了社会经济地位的影响后，这种影响仍然存在，这是一个重要的混杂因素（chi（2）= 83.89，df = 1; p = 5.2 x 10（-20））。然而，人群之间存在高度异质性：虽然大多数人群样本的效应方向是一致的，但人群之间的效应大小差异显着。这很可能反映了真正的生物异质性：是否可以观察到效应将取决于群体中纯合性的方差和个体隐性基因型的偶然遗传。这些结果预测了多个罕见的隐性变异影响人类身高。虽然这项探索性工作的重点是身高，开发的方法是普遍适用于遗传的数量性状（QT），铺平了道路的调查近交效应，因此遗传结构，对生物医学的重要性QT的范围。
Stature is a classical and highly heritable complex trait, with 80%-90% of variation explained by genetic factors. In recent years, genome-wide association studies (GWAS) have successfully identified many common additive variants influencing human height; however, little attention has been given to the potential role of recessive genetic effects. Here, we investigated genome-wide recessive effects by an analysis of inbreeding depression on adult height in over 35,000 people from 21 different population samples. We found a highly significant inverse association between height and genome-wide homozygosity, equivalent to a height reduction of up to 3 cm in the offspring of first cousins compared with the offspring of unrelated individuals, an effect which remained after controlling for the effects of socio-economic status, an important confounder (chi(2) = 83.89, df = 1; p = 5.2 x 10(-20)). There was, however, a high degree of heterogeneity among populations: whereas the direction of the effect was consistent across most population samples, the effect size differed significantly among populations. It is likely that this reflects true biological heterogeneity: whether or not an effect can be observed will depend on both the variance in homozygosity in the population and the chance inheritance of individual recessive genotypes. These results predict that multiple, rare, recessive variants influence human height. Although this exploratory work focuses on height alone, the methodology developed is generally applicable to heritable quantitative traits (QT), paving the way for an investigation into inbreeding effects, and therefore genetic architecture, on a range of QT of biomedical importance.