Sibling Fixed-Effects Design

The sibling fixed-effects, or sibling-comparison, design controls for everything that siblings share by construction. Genes (on average half), parents, household income, neighborhood, schooling, and family culture are differenced out when you compare brothers or sisters who differ in an exposure, so the residual within-family association is purged of all confounders common to the family. D'Onofrio, Lahey, Turkheimer, and Lichtenstein championed these family-based quasi-experiments as a way to integrate genetic and social-science research by rigorously testing competing causal hypotheses. Frisell and colleagues, however, gave the design its essential warning label: precisely because shared confounding is removed, the within-family estimate is unusually vulnerable to the confounders siblings do not share and to attenuation from measurement error. The design is powerful but double-edged.