title: Follow-up study of the first genome-wide association scan in alopecia areata: IL13 and KIAA0350 as susceptibility loci supported with genome-wide significance.
abstract: Recently, the first genome-wide association study (GWAS) of alopecia areata (AA) was conducted in a North-American sample, and this identified eight susceptibility loci surpassing genome-wide significance. The aim of the present follow-up association analysis was to confirm five of these eight loci (single-nucleotide polymorphisms (SNPs) from the CTLA4, IL-2RA, and HLA regions were not included due to previous own findings) and test 12 other loci from the GWAS, which did not surpass the threshold for genome-wide significance. Twenty-three SNPs from the 17 loci were investigated using a sample of 1,702 Central European AA patients and 1,723 controls. Of the five loci with previously reported genome-wide significance, association was confirmed for all of these: ULBP3/ULBP6, PRDX5, IL-2/IL-21, STX17, and IKZF4/ERBB3 (P-value <0.05). To detect robust evidence for association among the 12 other loci, a meta-analysis of the present association data and the data of the recent GWAS was performed. Genome-wide significant association was found for rs20541 (P(comb)=7.52 × 10(-10); odds ratio (OR)=1.30 (1.23-1.38)) and rs998592 (P(comb)=1.11 × 10(-11); OR=1.28 (1.21-1.36)), thus establishing IL-13 and KIAA0350/CLEC16A as susceptibility loci for AA. Interestingly, IL-13 and KIAA0350/CLEC16A are susceptibility loci for other autoimmune diseases, supporting the hypothesis of shared pathways of autoimmune susceptibility.
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Dagny
authors.initials: D
authors.lastname: Jagielska
authors.forename: Silke
authors.initials: S
authors.lastname: Redler
authors.forename: Felix F
authors.initials: FF
authors.lastname: Brockschmidt
authors.forename: Christine
authors.initials: C
authors.lastname: Herold
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Pasternack
authors.forename: Natalie
authors.initials: N
authors.lastname: Garcia Bartels
authors.forename: Sandra
authors.initials: S
authors.lastname: Hanneken
authors.forename: Sibylle
authors.initials: S
authors.lastname: Eigelshoven
authors.forename: Melanie
authors.initials: M
authors.lastname: Refke
authors.forename: Sandra
authors.initials: S
authors.lastname: Barth
authors.forename: Kathrin A
authors.initials: KA
authors.lastname: Giehl
authors.forename: Roland
authors.initials: R
authors.lastname: Kruse
authors.forename: Gerhard
authors.initials: G
authors.lastname: Lutz
authors.forename: Hans
authors.initials: H
authors.lastname: Wolff
authors.forename: Bettina
authors.initials: B
authors.lastname: Blaumeiser
authors.forename: Markus
authors.initials: M
authors.lastname: Böhm
authors.forename: Ulrike
authors.initials: U
authors.lastname: Blume-Peytavi
authors.forename: Tim
authors.initials: T
authors.lastname: Becker
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Regina C
authors.initials: RC
authors.lastname: Betz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000506:Alopecia Areata / Q000235:genetics*; D001327:Autoimmune Diseases / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics*; D037181:Lectins, C-Type / Q000235:genetics*; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: C522505:CLEC16A protein, human; D018793:Interleukin-13; D037181:Lectins, C-Type; D009004:Monosaccharide Transport Proteins