Alopecia areata (AA) is a genetically determined, immune-mediated disorder of the hair follicle that affects 1%-2% of the U.S. population. It is defined by a spectrum of severity that ranges from patchy localized hair loss on the scalp to the complete absence of hair everywhere on the body. In an effort to define the genetic basis of AA, we performed a genomewide search for linkage in 20 families with AA consisting of 102 affected and 118 unaffected individuals from the United States and Israel. Our analysis revealed evidence of at least four susceptibility loci on chromosomes 6, 10, 16 and 18, by use of several different statistical approaches. Fine-mapping analysis with additional families yielded a maximum multipoint LOD score of 3.93 on chromosome 18, a two-point affected sib pair (ASP) LOD score of 3.11 on chromosome 16, several ASP LOD scores >2.00 on chromosome 6q, and a haplotype-based relative risk LOD of 2.00 on chromosome 6p (in the major histocompatibility complex locus). Our findings confirm previous studies of association of the human leukocyte antigen locus with human AA, as well as the C3H-HeJ mouse model for AA. Interestingly, the major loci on chromosomes 16 and 18 coincide with loci for psoriasis reported elsewhere. These results suggest that these regions may harbor gene(s) involved in a number of different skin and hair disorders.
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We thank all participating families for their contribution to this study. We are deeply appreciative of the constant support and encouragement of the National Alopecia Areata Foundation (NAAF), and particularly Vicki Kalabokes, NAAF Executive Director. We are also grateful to the National Alopecia Areata Registry for its invaluable contributions and HaMut Lam for her expert technical assistance. This work was supported in part by grants from the NAAF (to A.M.C. and A.Z.), Israeli Alopecia Areata Fund (to A.Z.), Columbia University Clinical Trials Office Pilot Award (to A.M.-M.), the North American Hair Research Society Mentorship Award (to A.M.-M.), and the National Institutes of Health: National Institute of Arthritis and Musculoskeletal and Skin Diseases grants N01AR02249 (AA Registry [to M.D.]), R03AR050158 (to A.M-M. and J.M.), and R01AR52579 (to A.M.C.) and National Institute of Mental Health grant R01MH44292 (to J.O.).