Khoury and Flanders described the synergy index additive model for gene-environment studies. This can identify a situation when the odds ratio of an event with two risk factors is greater than the sum of the odd ratios for the individual risk factors. The authors are from the Centers for Disease Control and Prevention in Atlanta.
Study: Case control study to detect interaction between a risk factor and a genetic susceptibility factor
Situation
Cases
Controls
Odds Ratio
not exposed
genotype negative
X1
Y1
1.0
not exposed
genotype positive
X2
Y2
OR(genotype only)
exposed
genotype negative
X3
Y3
OR(exposure only)
exposed
genotype positive
X4
Y4
OR(combined)
odds ratio (genotype only) =
= (Y1 * X2) / (Y2 * X1)
odds ratio (exposure only) =
= (Y1 * X3) / (Y3 * X1)
odds ratio (combined) =
= (Y1 * X4) / (Y4 * X1)
(odds ratio combined) <relation>
((odds ratio exposure only) + (odds ratio genotype only) -1
<Relation>
Interpretation
>
interaction more than additive (synergy)
=
interaction additive (sum of parts)
<
interaction less than additive (interference)
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