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Revisiting heritability accounting for shared environmental effects and maternal inheritance

机译:重新考虑遗传力,以解决共同的环境影响和母体遗传问题

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摘要

Heritability measures the proportion of phenotypic variation attributable to genetic factors. In addition to a shared nuclear genetic component, a number of additional variance components, such as spousal correlation, sibship, household and maternal effects, may have strong contributions to inter-individual phenotype variation. In humans, the confounding effects of these components on heritability have not been studied thoroughly. We sought to obtain unbiased heritability estimates for complex traits in the presence of multiple variance components and also to estimate the contributions of these variance components to complex traits. We compared regression and variance component methods to estimate heritability in simulations when additional variance components existed. We then revisited heritability for several traits in Framingham Heart Study (FHS) participants. Using simulations, we found that failure to account for or misclassification of necessary variance components yielded biased heritability estimates. The direction and magnitude of the bias varied depending on a variance structure and an estimation method. Using the best fitted models to account for necessary variance components, we found that heritability estimates for most FHS traits were overestimated, ranging from 4 to 47 %, when we compared models that considered necessary variance components to models that only considered familial relationships. Spousal correlation explained 14-36 % of phenotypic variation in several anthropometric and lifestyle traits. Maternal and sibling effects also contributed to phenotypic variation, ranging from 3 to 5 % and 4 to 7 %, respectively, in several anthropometric and metabolic traits. Our findings may explain, in part, the missing heritability for some traits.
机译:遗传力衡量归因于遗传因素的表型变异的比例。除了共有的核遗传成分外,许多其他方差成分,例如配偶相关性,同居关系,家庭和母体影响,也可能对个体之间的表型变异有重要贡献。在人类中,尚未彻底研究这些成分对遗传力的混杂影响。我们试图在存在多个方差成分的情况下获得复杂性状的无偏遗传力估计,并估计这些方差成分对复杂性状的贡献。当存在额外的方差成分时,我们比较了回归和方差成分方法以估计模拟中的遗传力。然后,我们在弗雷明汉心脏研究(FHS)参与者中重新探究了几个性状的遗传力。使用模拟,我们发现无法解释或错误分类必要的方差分量会导致有偏的遗传力估计。偏差的方向和大小根据方差结构和估计方法而变化。使用最佳拟合模型来说明必要的方差成分时,我们发现,当我们将考虑必要方差成分的模型与仅考虑家庭关系的模型进行比较时,大多数FHS性状的遗传力估计被高估了,介于4%至47%之间。配偶相关性解释了几种人体测量学和生活方式特征中表型变异的14-36%。母体和兄弟姐妹的影响也促成表型变异,在一些人体测量和代谢特征中,变异分别为3%至5%和4%至7%。我们的发现可能部分解释了某些性状的遗传力缺失。

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