How to interpret a genome-wide association study
How to interpret a genome-wide association study
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DOI：
10.1001/jama.299.11.1335
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发表时间：
2008-03-19
影响因子：
120.7
通讯作者：
Manolio, Teri A.
中科院分区：
文献类型：
--
作者：
Pearson, Thomas A.;Manolio, Teri A.
全基因组关联（GWA）研究使用高通量基因分型技术来分析数十万个单核苷酸多态性（SNP），并将它们与临床状况和可测量的性状相关联。自2005年以来，在GWA研究中已经确定并复制了多达40种常见疾病和性状的近100个基因座，其中许多基因先前未被怀疑在所研究的疾病中起作用，还有一些基因组区域不含已知基因。GWA研究是发现影响疾病的遗传变异的重要进展，但也有重要的局限性，包括其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倚。虽然这些研究显然是从实际的临床应用中去除许多步骤，并且GWA发现在预防和治疗中的具体应用正在积极进行中，但目前这些研究主要代表了用于检查基因组功能和澄清病理生理机制的有价值的发现工具。本文介绍了GWA研究的设计，解释，应用和局限性，为临床医生和科学家，这一不断发展的科学可能有很大的相关性。
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.