Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis:
Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Here we show that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis. These variants are carried by ~9% of people of European origin. These variants also show highly significant association with asthma occurring in the context of atopic dermatitis.
This hits close to home, asthma and eczema both run in my family (atopic dermatitis). Now, why would a loss-of-function genetic variation exist at such a high frequency? One could posit that functional constraint was removed...but I can tell you from personal experiences that neither asthma nor eczema are "neutral." Of course, in the pre-modern world the environmental factors which result in the expression of both phenotypes might not have been present....
Poll on whether you have asthma or eczema in your "family" (defined as out to 1st cousins and up to grandparents):
