title: Assessment of the genetic basis of rosacea by genome-wide association study.
abstract: Rosacea is a common, chronic skin disease that is currently incurable. Although environmental factors influence rosacea, the genetic basis of rosacea is not established. In this genome-wide association study, a discovery group of 22,952 individuals (2,618 rosacea cases and 20,334 controls) was analyzed, leading to identification of two significant single-nucleotide polymorphisms (SNPs) associated with rosacea, one of which replicated in a new group of 29,481 individuals (3,205 rosacea cases and 26,262 controls). The confirmed SNP, rs763035 (P=8.0 × 10(-11) discovery group; P=0.00031 replication group), is intergenic between HLA-DRA and BTNL2. Exploratory immunohistochemical analysis of HLA-DRA and BTNL2 expression in papulopustular rosacea lesions from six individuals, including one with the rs763035 variant, revealed staining in the perifollicular inflammatory infiltrate of rosacea for both proteins. In addition, three HLA alleles, all MHC class II proteins, were significantly associated with rosacea in the discovery group and confirmed in the replication group: HLA-DRB1*03:01 (P=1.0 × 10(-8) discovery group; P=4.4 × 10(-6) replication group), HLA-DQB1*02:01 (P=1.3 × 10(-8) discovery group; P=7.2 × 10(-6) replication group), and HLA-DQA1*05:01 (P=1.4 × 10(-8) discovery group; P=7.6 × 10(-6) replication group). Collectively, the gene variants identified in this study support the concept of a genetic component for rosacea, and provide candidate targets for future studies to better understand and treat rosacea.
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Redwood City, California, USA. Electronic address: alschang@stanford.edu.
authors.forename: Anne Lynn S
authors.initials: ALS
authors.lastname: Chang
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Redwood City, California, USA.
authors.forename: Inbar
authors.initials: I
authors.lastname: Raber
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Redwood City, California, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Redwood City, California, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Redwood City, California, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Spitale
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Redwood City, California, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Chen
authors.affiliation: 23andMe Inc., Mountain View, California, USA.
authors.forename: Amy K
authors.initials: AK
authors.lastname: Kiefer
authors.affiliation: 23andMe Inc., Mountain View, California, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Tian
authors.affiliation: 23andMe Inc., Mountain View, California, USA.
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Eriksson
authors.affiliation: 23andMe Inc., Mountain View, California, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Hinds
authors.affiliation: 23andMe Inc., Mountain View, California, USA.
authors.forename: Joyce Y
authors.initials: JY
authors.lastname: Tung
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D059848:HLA-DQ alpha-Chains / Q000235:genetics; D059866:HLA-DQ beta-Chains / Q000235:genetics; D059811:HLA-DRB1 Chains / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011786:Quality Control; D012393:Rosacea / Q000235:genetics* / Q000378:metabolism
chemical_list: D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen; D000949:Histocompatibility Antigens Class II