Replicating genotype-phenotype associations
Replicating genotype-phenotype associations
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DOI：
10.1038/447655a
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发表时间：
2007-06-07
期刊：
影响因子：
64.8
通讯作者：
Collins, Francis S.
中科院分区：
文献类型：
--
作者：
Chanock, Stephen J.;Manolio, Teri;Collins, Francis S.
对任何关联的初步研究都是一个重要的发现工具。在不久的将来，一项研究不可能明确地建立有效的基因型-表型关联，而不需要重复。在确定初始全基因组或候选基因研究中的发现是否值得后续复制研究时，应考虑与研究设计和报告相关的一些要点（框2）。由于初始报告中缺乏方法学细节或原始研究中缺乏方法学严谨性，复制已报道的关联的尝试往往会变得复杂。由于在每个全基因组研究中测试了大量的基因型-表型关联，除非应用严格的统计阈值，否则虚假关联将大大超过真实关联。虽然不能在所有情况下为统计显著性指定通用阈值，但较小的p值通常为真实关联提供更大的支持。然而，极小的p值应该仔细解释，直到完成复制研究，因为
The initial study of any association represents an important discovery tool. In the near future, it is unlikely that a single study will unequivocally establish a valid genotype–phenotype association and not require replication. A number of points relating to the study design and reporting should be considered in determining whether a finding in an initial genomewide or candidate-gene study merits follow-up replication studies (Box 2). Attempts to replicate a reported association are often complicated by lack of methodological detail in the initial report or lack of methodological rigour in the original study.Because of the enormous number of genotype–phenotype associations tested in each genome-wide study, spurious associations will substantially outnumber true ones unless rigorous statistical thresholds are applied. Although no universal threshold can be specified for statistical significance in all circumstances, smaller P-values generally provide greater support for a true association. Extremely small P-values should be interpreted carefully, however, until completion of replication studies, because