Are filaggrin mutations associated with hand eczema or contact allergy? – we do not know

Conflicts of interest: none declared. Sir, We were interested to read the recent report by Lerbaek et al. describing their investigation of the association between filaggrin loss‐of‐function mutations and hand eczema or contact dermatitis.1 The study addresses an important question: filaggrin is known to play a significant role in epidermal barrier function and filaggrin null mutations result in deficiency or absence of filaggrin in the skin,2 so do these mutations also predispose to hand eczema and allergic sensitization? However, unfortunately the study design – specifically the choice of controls and lack of statistical power – means that this study is unable to give an answer to the question. These limitations are acknowledged by the authors but are not reflected in the title or abstract of their paper. Genetic association studies require careful phenotype definition and the matching of cases with an appropriate control population.3 This is particularly important for the investigation of a complex trait,4 where multiple genetic factors must be identified on a background of multiple environmental factors which all contribute to the pathogenesis of disease.