Skolkovo Institute of Science and Technology, Moscow, Russia.
Novosibirsk State University, Novosibirsk, Russia.
Eur J Hum Genet. 2021 Jul;29(7):1082-1091. doi: 10.1038/s41431-021-00836-7. Epub 2021 Mar 4.
Adult height inspired the first biometrical and quantitative genetic studies and is a test-case trait for understanding heritability. The studies of height led to formulation of the classical polygenic model, that has a profound influence on the way we view and analyse complex traits. An essential part of the classical model is an assumption of additivity of effects and normality of the distribution of the residuals. However, it may be expected that the normal approximation will become insufficient in bigger studies. Here, we demonstrate that when the height of hundreds of thousands of individuals is analysed, the model complexity needs to be increased to include non-additive interactions between sex, environment and genes. Alternatively, the use of log-normal approximation allowed us to still use the additive effects model. These findings are important for future genetic and methodologic studies that make use of adult height as an exemplar trait.
成人身高激发了第一批生物计量和定量遗传学研究，并成为理解遗传力的典型特征。对身高的研究导致了经典多基因模型的形成，该模型对我们理解和分析复杂特征的方式产生了深远的影响。经典模型的一个重要部分是假设效应的可加性和残差分布的正态性。然而，可以预期，在更大的研究中，正态逼近将变得不充分。在这里，我们证明了当分析数十万人的身高时，需要增加模型的复杂性，以包括性别、环境和基因之间的非加性相互作用。或者，使用对数正态逼近允许我们仍然使用加性效应模型。这些发现对于未来利用成人身高作为范例特征的遗传和方法学研究非常重要。
