A relatively new design also avoids use of population-based controls, but uses the parents of cases to serve as genetic controls, who are ethnically matched to each case [8]. One studies triads consisting of affected individuals and their parents. The notion is that genetic variants that confer susceptibility will have been over-transmitted to people with disease (compared to Mendelian transmission), and the extent of that over-transmission allows us to estimate the genetic relative risks [9]. This approach offers robustness against the bias due to population stratification that can affect a case-control approach to studying genetic risk factors. It also allows detection of maternally-mediated genetic effects [10] and parent-of-origin effects [11]. Stratification on exposure also permits estimation of multiplicative interaction parameters, by testing whether the genetic relative risks are the same across levels of the exposure. Clearly, this design relies on the adequate availability of parents and is best if used for conditions with onset early in life, such as birth defects. Although genetic main effects can now be estimated, a limitation is that because one cannot estimate the main effects
