Genetic studies of complex traits often show disparities in estimated heritability depending on the method used, whether by genomic associations or twin and family studies. We present a simulation of individual genomes with dynamic environmental conditions to consider how linear and nonlinear effects, gene-by-environment interactions, and gene-by-environment correlations may work together to govern the long-term development of complex traits and affect estimates of heritability from common methods. Our simulation studies demonstrate that the genetic effects estimated by genome wide association studies in unrelated individuals are inadequate to characterize gene-by-environment interaction, while including related individuals in genome-wide complex trait analysis (GCTA) allows gene-by-environment interactions to be recovered in the heritability. These theoretical findings provide an explanation for the “missing heritability” problem and bridge the conceptual gap between the most common findings of GCTA and twin studies. Future studies may use the simulation model to test hypotheses about phenotypic complexity either in an exploratory way or by replicating well-established observations of specific phenotypes.

复杂性状的遗传研究通常显示估计遗传力的差异取决于所使用的方法，无论是基因组关联还是双胞胎和家庭研究。我们展示了对具有动态环境条件的个体基因组的模拟，以考虑线性和非线性效应、基因与环境的相互作用以及基因与环境的相关性如何共同作用来控制复杂性状的长期发展并影响对常用方法的遗传性。我们的模拟研究表明，通过全基因组关联研究估计的不相关个体的遗传效应不足以描述基因与环境的相互作用，而将相关个体纳入全基因组复杂性状分析 (GCTA) 允许基因与环境的相互作用在遗传力中得到恢复。这些理论发现为“遗传力缺失”问题提供了解释，并弥合了 GCTA 和双胞胎研究最常见发现之间的概念鸿沟。未来的研究可能会使用模拟模型以探索性方式或通过复制对特定表型的既定观察来检验关于表型复杂性的假设。