The Center for Applied Genomics and Division of Human Genetics, The Children's Hospital of Philadelphia Research Institute, PA, USA.
Ann Med. 2011;43(6):451-60. doi: 10.3109/07853890.2011.573803. Epub 2011 May 19.
It is well established that genetic diversity combined with specific environmental exposures contributes to disease susceptibility. However, it has turned out to be challenging to isolate the genes underlying the genetic component conferring susceptibility to most complex disorders. Traditional candidate gene and family-based linkage studies, which dominated gene discovery efforts for many years, were largely unsuccessful in unraveling the genetics of these traits due to the relatively limited information gained. Within the last 5 years, new advances in high-throughput methods have allowed for large volumes of single nucleotide polymorphisms (SNPs) throughout the genome to be genotyped across large and comprehensively phenotyped patient cohorts. Unlike previous approaches, these 'genome-wide association studies' (GWAS) have extensively delivered on the promise of uncovering genetic determinants of complex diseases, with hundreds of novel disease-associated variants being largely replicated by independent groups. This review provides an overview of these recent breakthroughs in the context of the pitfalls and challenges related to designing and carrying out a successful GWAS.
众所周知，遗传多样性与特定的环境暴露相结合，导致了疾病易感性。然而，要分离出导致大多数复杂疾病易感性的遗传因素，这已经被证明是具有挑战性的。多年来，传统的候选基因和基于家族的连锁研究主导了基因发现工作，但由于获得的信息相对有限，在揭示这些特征的遗传学方面，这些研究基本上都没有成功。在过去的 5 年中，高通量方法的新进展使得可以对基因组中的大量单核苷酸多态性（SNPs）进行基因分型，跨越大型和全面表型患者队列。与以前的方法不同，这些“全基因组关联研究”（GWAS）在揭示复杂疾病的遗传决定因素方面取得了广泛的成功，数以百计的新的与疾病相关的变异被独立的研究小组大量复制。这篇综述概述了这些最近的突破，同时也讨论了设计和进行成功的 GWAS 相关的陷阱和挑战。
