Other, as yet unreplicated disease-modifier SNPs have been reported.
We interpret these correlations to mean that there are modifier SNPs that affect but are not completely responsible for the phenotype of that event.
Thus, it is common for events to have one (or more) small, modifier SNPs that are below the significance cutoff of 0.244, where we are unable to detect them (Figure 4G).
However, we have shown previously that modifier SNPs in combination can result in large differences in the absolute risk of developing breast cancer for carriers at the extreme percentiles of the combined SNP distribution [ 5, 39].
Conceived as a modifier SNP, the present results suggest that rs16965628 predicts brain activity related to the disruption of cognitive control by emotional or traumatic information in the ventrolateral prefrontal cortex.
However, for most chemotherapeutics, toxicity and response are probably multigenic traits, dependent on multiple SNPs in modifier genes that have small effect sizes.
No evidence of association was found when the larger series was analysed which lead us to conclude that none of the three SNPs are significant modifiers of breast cancer risk for mutation carriers.
However, as there was no adjustment for multiple testing in this study, these results are to be viewed as preliminary, and further research is warranted to explore the role of these common SNPs as 'effect modifiers' in dietary intervention studies to improve plasma lipids and apolipoproteins.
While SNP changes must be upstream (causal) of gene expression and phenotype manifestations, this does not preclude some SNPs from modifying the action of other SNPs, and the effect of such modifiers may become apparent only in particular contexts.
CIMBA = Consortium of Investigators of Modifiers of BRCA1 and BRCA2; SNP = single nucleotide polymorphism.
