Moutsianas Loukas, Morris Andrew P
Brief Funct Genomics. 2014 Sep;13(5):362-70. doi: 10.1093/bfgp/elu012. Epub 2014 Jun 10.
Genome-wide association studies have been successful in identifying common variants that impact complex human traits and diseases. However, despite this success, the joint effects of these variants explain only a small proportion of the genetic variance in these phenotypes, leading to speculation that rare genetic variation might account for much of the 'missing heritability'. Consequently, there has been an exciting period of research and development into the methodology for the analysis of rare genetic variants, typically by considering their joint effects on complex traits within the same functional unit or genomic region. In this review, we describe a general framework for modelling the joint effects of rare genetic variants on complex traits in association studies of unrelated individuals. We summarise a range of widely used association tests that have been developed from this model and provide an overview of the relative performance of these approaches from published simulation studies.
全基因组关联研究已成功识别出影响复杂人类性状和疾病的常见变异。然而，尽管取得了这一成功，但这些变异的联合效应仅解释了这些表型中一小部分的遗传变异，这引发了一种推测，即罕见遗传变异可能是大部分“缺失遗传力”的原因。因此，在罕见遗传变异分析方法的研究和开发方面出现了一个令人兴奋的时期，通常是通过考虑它们对同一功能单元或基因组区域内复杂性状的联合效应来进行。在本综述中，我们描述了一个用于在无关个体的关联研究中对罕见遗传变异对复杂性状的联合效应进行建模的通用框架。我们总结了一系列基于该模型开发的广泛使用的关联检验，并从已发表的模拟研究中概述了这些方法的相对性能。
