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Am J Hum Genet. 2007 Mar;80(3):531-8. Epub 2007 Jan 22.

No gene is an island: the flip-flop phenomenon.

Author information

  • 1Center for Human Genetics, Duke University Medical Center, Durham, NC, USA.

Erratum in

  • Am J Hum Genet. 2007 May;80(5):1002.


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.

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