Pearson Thomas A, Manolio Teri A
Office of Population Genomics, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892-2154, USA.
JAMA. 2008 Mar 19;299(11):1335-44. doi: 10.1001/jama.299.11.1335.
Genome-wide association (GWA) studies use high-throughput genotyping technologies to assay hundreds of thousands of single-nucleotide polymorphisms (SNPs) and relate them to clinical conditions and measurable traits. Since 2005, nearly 100 loci for as many as 40 common diseases and traits have been identified and replicated in GWA studies, many in genes not previously suspected of having a role in the disease under study, and some in genomic regions containing no known genes. GWA studies are an important advance in discovering genetic variants influencing disease but also have important limitations, including their potential for false-positive and false-negative results and for biases related to selection of study participants and genotyping errors. Although these studies are clearly many steps removed from actual clinical use, and specific applications of GWA findings in prevention and treatment are actively being pursued, at present these studies mainly represent a valuable discovery tool for examining genomic function and clarifying pathophysiologic mechanisms. This article describes the design, interpretation, application, and limitations of GWA studies for clinicians and scientists for whom this evolving science may have great relevance.
全基因组关联（GWA）研究使用高通量基因分型技术来检测数十万单核苷酸多态性（SNP），并将它们与临床病症和可测量性状联系起来。自2005年以来，在GWA研究中已识别并重复验证了近100个与多达40种常见疾病和性状相关的基因座，其中许多位于先前未怀疑与所研究疾病有关的基因中，还有一些位于不包含已知基因的基因组区域。GWA研究在发现影响疾病的遗传变异方面是一项重要进展，但也存在重要局限性，包括出现假阳性和假阴性结果的可能性，以及与研究参与者选择和基因分型错误相关的偏差。尽管这些研究显然距离实际临床应用还有很多步骤，并且正在积极探索GWA研究结果在预防和治疗方面的具体应用，但目前这些研究主要是用于检验基因组功能和阐明病理生理机制的有价值的发现工具。本文为临床医生和科学家描述了GWA研究的设计、解读、应用及局限性，这一不断发展的科学可能与他们密切相关。
