Mayhew Alexandra J, Meyre David
Department of Health Research Methods, McMaster University, Evidence and Impact, Hamilton, Ontario, Canada.
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Curr Genomics. 2017 Aug;18(4):332-340. doi: 10.2174/1389202918666170307161450.
The goal of this review article is to provide a conceptual based summary of how heritability estimates for complex traits such as obesity are determined and to explore the future directions of research in the heritability field. The target audience are researchers who use heritability data rather than those conducting heritability studies. The article provides an introduction to key concepts critical to understanding heritability studies including: i) definitions of heritability: broad sense versus narrow sense heritability; ii) how data for heritability studies are collected: twin, adoption, family and population-based studies; and iii) analytical techniques: path analysis, structural equations and mixed or regressive models of complex segregation analysis. For each section, a discussion of how the different definitions and methodologies influence heritability estimates is provided. The general limitations of heritability studies are discussed including the issue of "missing heritability" in which heritability estimates are significantly higher than the variance explained by known genetic variants. Potential causes of missing heritability include restriction of many genetic association studies to single nucleotide polymorphisms, gene by gene interactions, epigenetics, and gene by environment interactions. Innovative strategies of accounting for missing heritability including modeling techniques and improved software are discussed.
这篇综述文章的目的是基于概念对肥胖等复杂性状的遗传力估计如何确定进行总结，并探讨遗传力领域的未来研究方向。目标受众是使用遗传力数据的研究人员，而非进行遗传力研究的人员。文章介绍了理解遗传力研究至关重要的关键概念，包括：i）遗传力的定义：广义遗传力与狭义遗传力；ii）遗传力研究数据的收集方式：双胞胎、收养、家庭和基于人群的研究；iii）分析技术：路径分析、结构方程以及复杂分离分析的混合或回归模型。对于每个部分，都讨论了不同定义和方法如何影响遗传力估计。还讨论了遗传力研究的一般局限性，包括“遗传力缺失”问题，即遗传力估计显著高于已知基因变异所解释的方差。遗传力缺失的潜在原因包括许多基因关联研究局限于单核苷酸多态性、基因与基因的相互作用、表观遗传学以及基因与环境的相互作用。文中还讨论了考虑遗传力缺失的创新策略，包括建模技术和改进的软件。
