Commentary: Advent of sibling designs

The rapidly increasing use of sibling comparisons is a welcome development in epidemiology. Although sibling designs have been used by epidemiologists since the mid-20th century, contemporary researchers are extending the range of applications, clarifying appropriate methods1 and introducing novel strategies. The proliferation of sibling studies has not been matched, however, by comparable progress towards a conceptual framework that gives coherence to the new array of approaches. We propose that, as a starting point for a conceptual framework, a fundamental distinction be made between designs that assume a ‘stable’ vs ‘dynamic’ family context. Designs that assume a stable family context exploit the fact that siblings share stable aspects of family context as well as half their genome. In ‘sibling discordance’ studies, for example, we compare outcomes among siblings who are discordant for an exposure of interest, and we want the siblings to be as similar as possible in family context and genetic predisposition. Differences between siblings in family context are potential confounders, and, when measured (e.g. birth order), are controlled in the analyses. Influences of family members upon one another are generally disregarded. In contrast, designs that assume a dynamic family context exploit the fact that siblings and other family members influence each other in a variety of ways. In birth-order studies, for example, we compare outcomes among siblings who encounter different family contexts and may play a role in creating these contexts. Influences of family members upon one another, and the resulting changes in family context, are the topic of investigation. We hope to show that this distinction between sibling designs based on stable vs dynamic family context is readily understood, broadly applicable to traditional as well as novel approaches, and useful as a starting point. To this end, we portray a range of recent sibling studies, and consider them within this framework. Our overarching goal is to stimulate others to further elaborate the conceptual underpinnings of sibling designs.