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On sibling designs.

First, given that uncontrolled, unshared environmental factors can bias the results of siblingmatched studies, Frisell et al2 note that these aspects should be measured and controlled when possible. Usually discordant sibling studies do, however, control for systematic unshared aspects of the family environment that can be measured, for example, birth order, maternal and paternal age, and gestational age at birth. Furthermore, population estimates controlled for measured unshared aspects of the family environment often render similar estimates to the discordant sibling estimates. It is the nonsystematic aspects of the unshared environment that are most difficult to measure and that tend to be uncontrolled. But evidence suggests that these nonsystematic factors tend to be events that do not relate in any general way to confounding factors.3 Thus, after taking into account the way that discordant sibling studies are actually done, the extent to which their results will be biased by unshared factors remains unclear.