Abstract
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 dis-equilibrium, with a causal variant at another locus, and we show how these findings could explain previous reports of flip-flop associations.
| Original language | English |
|---|---|
| Pages (from-to) | 531-538 |
| Number of pages | 8 |
| Journal | American Journal of Human Genetics |
| Volume | 80 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2007 |
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ASJC Scopus subject areas
- Genetics
Cite this
No gene is an island : The flip-flop phenomenon. / Lin, Ping I.; Vance, Jeffery M; Pericak-Vance, Margaret A; Martin, Eden R.
In: American Journal of Human Genetics, Vol. 80, No. 3, 01.03.2007, p. 531-538.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - No gene is an island
T2 - The flip-flop phenomenon
AU - Lin, Ping I.
AU - Vance, Jeffery M
AU - Pericak-Vance, Margaret A
AU - Martin, Eden R
PY - 2007/3/1
Y1 - 2007/3/1
N2 - 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 dis-equilibrium, with a causal variant at another locus, and we show how these findings could explain previous reports of flip-flop associations.
AB - 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 dis-equilibrium, with a causal variant at another locus, and we show how these findings could explain previous reports of flip-flop associations.
UR - http://www.scopus.com/inward/record.url?scp=33847230623&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33847230623&partnerID=8YFLogxK
U2 - 10.1086/512133
DO - 10.1086/512133
M3 - Article
C2 - 17273975
AN - SCOPUS:33847230623
VL - 80
SP - 531
EP - 538
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 3
ER -