Center for Human Genetic Research and Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
Hum Mol Genet. 2012 Oct 15;21(R1):R1-9. doi: 10.1093/hmg/dds387. Epub 2012 Sep 13.
Genetic association and linkage studies can provide insights into complex disease biology, guiding the development of new diagnostic and therapeutic strategies. Over the past decade, genetic association studies have largely focused on common, easy to measure genetic variants shared between many individuals. These common variants typically have subtle functional consequence and translating the resulting association signals into biological insights can be challenging. In the last few years, exome sequencing has emerged as a cost-effective strategy for extending these studies to include rare coding variants, which often have more marked functional consequences. Here, we provide practical guidance in the design and analysis of complex trait association studies focused on rare, coding variants.
遗传关联和连锁研究可以深入了解复杂的疾病生物学，为新的诊断和治疗策略的发展提供指导。在过去的十年中，遗传关联研究主要集中在许多个体之间共享的常见、易于测量的遗传变异上。这些常见的变异通常具有微妙的功能后果，将由此产生的关联信号转化为生物学见解具有挑战性。在过去的几年中，外显子组测序已成为一种具有成本效益的策略，可以将这些研究扩展到包括罕见的编码变异，这些变异通常具有更明显的功能后果。在这里，我们提供了针对罕见编码变异的复杂性状关联研究的设计和分析的实用指南。
