Genetic linkage studies in alopecia areata.

Alopecia areata affects approximately 4.6 million individuals in the United States alone. It is typified by patchy hair loss on the scalp that can progress to cover the entire scalp (alopecia totalis) and eventually the entire body (alopecia universalis). Despite the high incidence of this condition, its genetic basis is largely unknown. It is now generally accepted, however, that it fits the paradigm of a complex trait, in which a combination of genetic and environmental factors results in the final phenotype. Genetic studies have been limited thus far to association analyses, which suggest that a permissive HLA status may potentiate the development of alopecia areata. A systematic screen for identifying the primary genetic mechanisms underlying this disorder has never before been undertaken, however. Here we discuss our approach to the identification of susceptibility genes for alopecia areata. In particular, we recently initiated a comprehensive genetic analysis by performing a genome-wide scan in a collection of alopecia families with multiple affected family members. There are currently a number of examples of complex diseases of the skin, such as psoriasis and atopic dermatitis, in which genetic studies are being undertaken that substantiate the timeliness of this approach. We anticipate that these studies will lead to the identification of the susceptibility genes and provide a foundation for understanding how they interact with each other and with other variables, such as the immune system and environmental factors.