[PDF][PDF] No gene is an island: the flip-flop phenomenon

PI Lin, JM Vance, MA Pericak-Vance… - The American Journal of …, 2007 - cell.com
The American Journal of Human Genetics, 2007cell.com
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 …
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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