Replication in genome-wide association studies.
Replication in genome-wide association studies.
复制标题
DOI：
10.1214/09-sts290
复制
发表时间：
2009-11-01
期刊：
影响因子：
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通讯作者：
Ioannidis JP
中科院分区：
文献类型：
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作者：
Kraft P;Zeggini E;Ioannidis JP
复制有助于确保在全基因组关联（GWA）研究中观察到的基因型-表型关联代表了一种可信的关联，而不是偶然发现或由于不受控制的偏差而产生的伪产物。我们讨论精确复制的先决条件；异质性问题；跨多个研究的不同数据合成方法的优缺点；频率论与贝叶斯推理的复制；以及多团队合作带来的挑战。虽然一致的复制可以极大地提高基因型-表型关联的可信度，但由于许多研究都存在偏差，因此可能无法消除虚假关联。相反，在有力的后续研究中，缺乏重复性通常会使最初提出的关联无效，尽管有时它可能指出连锁不平衡或效应修饰因子在研究中的差异。
Replication helps ensure that a genotype-phenotype association observed in a genome-wide association (GWA) study represents a credible association and is not a chance finding or an artifact due to uncontrolled biases. We discuss prerequisites for exact replication; issues of heterogeneity; advantages and disadvantages of different methods of data synthesis across multiple studies; frequentist vs. Bayesian inferences for replication; and challenges that arise from multi-team collaborations. While consistent replication can greatly improve the credibility of a genotype-phenotype association, it may not eliminate spurious associations due to biases shared by many studies. Conversely, lack of replication in well-powered follow-up studies usually invalidates the initially proposed association, although occasionally it may point to differences in linkage disequilibrium or effect modifiers across studies.