title: Genomewide scan for linkage reveals evidence of several susceptibility loci for alopecia areata.
abstract: 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.
authors.affiliation: Department of Dermatology, Columbia University, New York, NY 10032, USA.
authors.forename: Amalia
authors.initials: A
authors.lastname: Martinez-Mir
authors.forename: Abraham
authors.initials: A
authors.lastname: Zlotogorski
authors.forename: Derek
authors.initials: D
authors.lastname: Gordon
authors.forename: Lynn
authors.initials: L
authors.lastname: Petukhova
authors.forename: Jianhong
authors.initials: J
authors.lastname: Mo
authors.forename: T Conrad
authors.initials: TC
authors.lastname: Gilliam
authors.forename: Douglas
authors.initials: D
authors.lastname: Londono
authors.forename: Chad
authors.initials: C
authors.lastname: Haynes
authors.forename: Jurg
authors.initials: J
authors.lastname: Ott
authors.forename: Maria
authors.initials: M
authors.lastname: Hordinsky
authors.forename: Krassimira
authors.initials: K
authors.lastname: Nanova
authors.forename: David
authors.initials: D
authors.lastname: Norris
authors.forename: Vera
authors.initials: V
authors.lastname: Price
authors.forename: Madeleine
authors.initials: M
authors.lastname: Duvic
authors.forename: Angela M
authors.initials: AM
authors.lastname: Christiano
mesh_terms: D000506:Alopecia Areata / Q000235:genetics*; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D008297:Male; D010375:Pedigree