Verma Shefali Setia, Ritchie Marylyn D
The Huck Institute of Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Genes (Basel). 2018 Jan 25;9(2):61. doi: 10.3390/genes9020061.
A plethora of genetic association analyses have identified several genetic risk loci. Technological and statistical advancements have now led to the identification of not only common genetic variants, but also low-frequency variants, structural variants, and environmental factors, as well as multi-omics variations that affect the phenotypic variance of complex traits in a population, thus referred to as complex trait architecture. The concept of heritability, or the proportion of phenotypic variance due to genetic inheritance, has been studied for several decades, but its application is mainly in addressing the narrow sense heritability (or additive genetic component) from Genome-Wide Association Studies (GWAS). In this commentary, we reflect on our perspective on the complexity of understanding heritability for human traits in comparison to model organisms, highlighting another round of clues beyond GWAS and an alternative approach, investigating these clues comprehensively to help in elucidating the genetic architecture of complex traits.
大量的基因关联分析已经确定了多个遗传风险位点。技术和统计方面的进步现在不仅导致了常见遗传变异的识别，还包括低频变异、结构变异和环境因素，以及影响人群复杂性状表型变异的多组学变异，因此被称为复杂性状结构。遗传力的概念，即由于遗传继承导致的表型变异比例，已经研究了几十年，但其应用主要是在解决全基因组关联研究（GWAS）中的狭义遗传力（或加性遗传成分）。在这篇评论中，我们反思了与模式生物相比，我们对理解人类性状遗传力复杂性的观点，强调了GWAS之外的另一轮线索以及一种替代方法，即全面研究这些线索以帮助阐明复杂性状的遗传结构。
