The Genetic Architecture of Alopecia Areata

Abstract

A major impetus to initiating the Human Genome Project was the belief that information encoded in the human genome would "accelerate progress in understanding disease pathogenesis and in developing new approaches to diagnosis, treatment, and prevention in many areas of medicine". Alopecia areata (AA) is a notable example of how understanding the genetic basis of a disease can have an impact on the care of patients in a relatively short time. Our first genome-wide association study in AA identified an initial set of common variants that increase risk of AA, some of which are shared with other autoimmune diseases. Thus, there has already been rapid progress in the translation of this information into new therapeutic strategies for patients, as drugs are already on the market for some of these disorders that can now be tested in AA. Informed by the progress achieved with genetic studies for mechanistically aligned autoimmune diseases, we are poised to carry this work forward and interrogate the underlying disease mechanisms in AA. Importantly, future genetic studies aimed at identifying additional susceptibility genes will further establish the foundation for the application of precision medicine in the care of AA patients.

Alopecia areata

“…The initial genetic studies concentrated on single genes that were known to be involved in related autoimmune diseases. Interestingly, many of these genes did in fact play a role in alopecia areata in addition to inflammatory bowel disease, multiple sclerosis, psoriasis, and type 1 diabetes mellitus 51 . Owing to the focus on an autoimmune etiology, the HLA region, which encodes MHC molecules in humans, was initially identified as a major contributor to the alopecia areata phenotype 51–54 .…”

“…Interestingly, many of these genes did in fact play a role in alopecia areata in addition to inflammatory bowel disease, multiple sclerosis, psoriasis, and type 1 diabetes mellitus 51 . Owing to the focus on an autoimmune etiology, the HLA region, which encodes MHC molecules in humans, was initially identified as a major contributor to the alopecia areata phenotype 51–54 . The HLA region is one of the most gene-dense regions of the genome and encodes for key immune regulators 55 .…”

Evaluation of Hair Loss

“…A positive family history is typical of male and female pattern hair loss (androgenetic alopecia) and is often found in alopecia areata [1], where it is considered a negative prognostic factor. Inherited hair disorders may have an autosomal dominant or autosomal recessive inheritance, and tracing a pedigree of the family is mandatory to understand the transmission of the genetic trait in these cases.…”

Familial implications of autoimmune disease: Recurrence risks of alopecia areata and associated conditions in first‐degree relatives

“…Very little was known about the genetic aspects until fairly recently, when genetic markers associated with AA were identified through genome‐wide association studies (Petukhova et al, ). These genetic markers also overlap with other autoimmune disorders including multiple sclerosis, celiac disease, psoriasis, rheumatoid arthritis, and others (Petukhova & Christiano, ).…”