No gene is an island: The flip-flop phenomenon
No gene is an island: The flip-flop phenomenon
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DOI：
10.1086/512133
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发表时间：
2007-03-01
影响因子：
9.8
通讯作者：
Martin, Eden R.
中科院分区：
文献类型：
--
作者：
Lin, Ping-I;Vance, Jeffery M.;Martin, Eden R.
越来越多的出版物正在复制之前报道的疾病标志物关联，但风险等位基因与之前的报告相反。这种“反复无常”的关联是否证实或反驳了先前的关联发现？我们假设这些关联可能确实是证实，但多位点效应和位点间相关性的变化导致了这种翻转现象。我们使用理论模型来证明，当所研究的变异通过交互作用或连锁不平衡与另一个基因座的因果变异相关时，就会发生触发器关联，并且我们展示了这些发现如何解释之前关于触发器关联的报告。
An increasing number of publications are replicating a previously reported disease-marker association but with the risk allele reversed from the previous report. Do such "flip-flop" associations confirm or refute the previous association findings? We hypothesized that these associations may indeed be confirmations but that multilocus effects and variation in interlocus correlations contribute to this flip-flop phenomenon. We used theoretical modeling to demonstrate that flip-flop associations can occur when the investigated variant is correlated, through interactive effects or linkage disequilibrium, with a causal variant at another locus, and we show how these findings could explain previous reports of flip-flop associations.