Is the atopic march related to confounding by genetics and early-life environment? A systematic review of sibship and twin data.

A popular hypothesis known as the atopic march proposes a set of sequential allergy and respiratory disorders in early childhood contributes enormously to the burden of disease in developed countries. Although the concept of the atopic march has been refined and strengthened by many cross-sectional and longitudinal studies linking eczema as the initial manifestation with progression to hay fever and then asthma, there is yet no definitive proof that the atopic march is the primary causal factor in childhood allergic disease. This debate is mainly related to the controversy around potential confounding of these associations by genetic and environmental factors. Family studies are ideally suited to unravelling the role of these factors. While multiple reviews have synthesized evidence from studies investigating this question, no review to date has explored specific evidence generated by twin and sibling studies to understand the aetiology of atopic march diseases. Our aim was to conduct a systematic review of twin and sibling studies that examine the allergic phenotypes that form the atopic march, to determine whether such analyses of data from these studies attempt to control for the effect confounding by shared factors, and to report estimates of the magnitude of associations between multiple phenotypes. Our review suggests that (1) genetics play a bigger role predisposing eczema to hay fever and eczema to asthma than environmental factors, and (2) the link between eczema and asthma and hay fever is independent of shared early-life environmental factors.