IL10-592 CA genotype, and not the CC nor the AA genotypes, has been found to be associated with development of the disease. How can we explain this finding?
Expression of C is antagonist of expression of A ? is there any interaction between the products of IL10-592 ? what is the product when being AA ? what is the product when being CC ? I hope those question could help you in your interpretation.
There is an interesting paper regarding sodium channel SCN5A. Patch clamp experiments revealed a loss of function of the channel only when it is expressed mut/wt not mut/mut. The authors identified a dominant negative effect on cell surface expression only when expressed with wt. Good luck for your research.
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I would assume this to be a false-positive result, because heterozygote advantage is only rarely seen.
However, there are known examples of similar cases in the litterature. Probably one of the best known cases is that of sickling vs. malaria susceptibility (see: Roth EF Jr, Friedman M, Ueda Y, Tellez I, Trager W, Nagel RL. Sickling rates of human AS red cells infected in vitro with Plasmodium falciparum malaria. Science. 1978 Nov 10;202(4368):650-2.).
If it is not just a false-positive, it could also be another SNP in linkage disequilibrium with your candidate SNP that is the actual causative SNP.
One possibility is that it is the result of a dominant negative effect (as Martin has elaborated), however, this is quite a rare phenomenon.
The other (more likely) possibility is the effect of excess heterozygosity in the control group and this will give a strong p-value when comparing HETs in cases vs controls. The best way to be sure that the association is NOT a false positive (as mentioned by Christian) is to check HWE in the control group and see if there is any significant deviation. If that is the case, one possible reason for this is the 'isolate breaking effect'; the control group does not represent a single random-mating population.
We have addressed this issue in our paper where we think false positive associations have been reported:
https://www.researchgate.net/publication/280328698_The_Essentiality_of_Reporting_Hardy-Weinberg_Equilibrium_Calculations_in_Population-Based_Genetic_Association_Studies
Hope it helps.
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