Molecular Genetics Laboratory, Eastern Health, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada.
Department of Medicine (Rheumatology), Memorial University of Newfoundland, St. John's, NL, Canada.
Methods Mol Biol. 2021;2249:335-367. doi: 10.1007/978-1-0716-1138-8_19.
Genetic and environmental factors are critical elements in most common complex disease. Genetics is increasingly being recognized to play a substantive role in the susceptibility, prognosis, and treatment of common diseases. Due to recent and rapid advancements in characterization of genetic variants and large-scale genotyping platforms, multiple genes and genetic variants have now been identified for common, complex diseases. The most efficient method for gene identification at present appears to be large-scale association-based studies, which integrate genetic and epidemiological principles. As the strategy for gene identification studies has shifted toward genetic association-based methods rather than traditional linkage analysis, epidemiological methods are increasingly being integrated into genetic investigations and in public health research. Consequently, the disciplines of genetics and epidemiology, which historically have functioned separately, have been integrated into a hybrid discipline referred to as genetic epidemiology. In this chapter, we review methods for establishing the genetic burden of complex genetic disease, followed by methods for gene and/or genetic variant identification. When appropriate, we will highlight the epidemiological issues and clinical applications that guide these methods.
遗传和环境因素是大多数常见复杂疾病的关键因素。遗传学越来越被认为在常见疾病的易感性、预后和治疗中发挥实质性作用。由于近年来对遗传变异和大规模基因分型平台的特征描述取得了迅速进展,现在已经确定了多种基因和遗传变异与常见复杂疾病有关。目前,基因鉴定最有效的方法似乎是基于大规模关联的研究,这些研究综合了遗传和流行病学原理。随着基因鉴定研究策略从传统的连锁分析转向基于遗传关联的方法,流行病学方法越来越多地被整合到遗传研究和公共卫生研究中。因此,历史上分别发挥作用的遗传学和流行病学这两个学科已经整合为一个称为遗传流行病学的混合学科。在本章中,我们回顾了确定复杂遗传性疾病遗传负担的方法,然后介绍了基因和/或遗传变异的鉴定方法。在适当的情况下,我们将重点介绍指导这些方法的流行病学问题和临床应用。