The common forms of metabolic diseases are highly complex, involving hundreds of genes, environmental and lifestyle factors, age-related changes, sex differences and gut–microbiome interactions. Systems genetics is a population-based approach to address this complexity. In contrast to commonly used ‘reductionist’ approaches, such as gain or loss of function, that examine one element at a time, systems genetics uses high-throughput ‘omics’ technologies to quantitatively assess the many molecular differences among individuals in a population and then to relate these to physiologic functions or disease states. Unlike genome-wide association studies, systems genetics seeks to go beyond the identification of disease-causing genes to understand higher-order interactions at the molecular level. The purpose of this review is to introduce the systems genetics applications in the areas of metabolic and cardiovascular disease. Here, we explain how large clinical and omics-level data and databases from both human and animal populations are available to help researchers place genes in the context of pathways and networks and formulate hypotheses that can then be experimentally examined. We provide lists of such databases and examples of the integration of reductionist and systems genetics data. Among the important applications emerging is the development of improved nutritional and pharmacological strategies to address the rise of metabolic diseases.

代谢疾病的常见形式非常复杂，涉及数百个基因、环境和生活方式因素、与年龄相关的变化、性别差异和肠道-微生物组的相互作用。系统遗传学是一种基于人群的方法来解决这种复杂性。与一次检查一个元素的常用“还原论”方法（例如功能的获得或丧失）相比，系统遗传学使用高通量“组学”技术来定量评估群体中个体之间的许多分子差异，然后将这些与生理功能或疾病状态联系起来。与全基因组关联研究不同，系统遗传学试图超越对致病基因的鉴定，以了解分子水平的高阶相互作用。本综述的目的是介绍系统遗传学在代谢和心血管疾病领域的应用。在这里，我们解释了来自人类和动物种群的大型临床和组学水平数据和数据库如何可用于帮助研究人员将基因置于通路和网络的背景下，并制定可以通过实验检验的假设。我们提供了此类数据库的列表以及还原论和系统遗传学数据整合的示例。新兴的重要应用之一是开发改进的营养和药理学策略以应对代谢疾病的增加。我们解释了来自人类和动物种群的大型临床和组学水平数据和数据库如何可用于帮助研究人员将基因置于通路和网络的背景下，并制定可以通过实验检验的假设。我们提供了此类数据库的列表以及还原论和系统遗传学数据整合的示例。新兴的重要应用之一是开发改进的营养和药理学策略以应对代谢疾病的增加。我们解释了来自人类和动物种群的大型临床和组学水平数据和数据库如何可用于帮助研究人员将基因置于通路和网络的背景下，并制定可以通过实验检验的假设。我们提供了此类数据库的列表以及还原论和系统遗传学数据整合的示例。新兴的重要应用之一是开发改进的营养和药理学策略以应对代谢疾病的增加。