No gene is an island: The flip-flop phenomenon

被引:398
作者
Lin, Ping-I [1 ]
Vance, Jeffery M. [1 ]
Pericak-Vance, Margaret A. [1 ]
Martin, Eden R. [1 ]
机构
[1] Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC USA
关键词
D O I
10.1086/512133
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
引用
收藏
页码:531 / 538
页数:8
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