A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1
Copyright policy )A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1
To identify new susceptibility loci for psoriasis, we undertook a genome-wide association study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified associations at eight previously unreported genomic loci. Seven loci harbored genes with recognized immune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These associations were replicated in 9,079 European samples (six loci with a combined P < 5 × 10⁻⁸ and two loci with a combined P < 5 × 10⁻⁷). We also report compelling evidence for an interaction between the HLA-C and ERAP1 loci (combined P = 6.95 × 10⁻⁶). ERAP1 plays an important role in MHC class I peptide processing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk allele. Our findings implicate pathways that integrate epidermal barrier dysfunction with innate and adaptive immune dysregulation in psoriasis pathogenesis.
- NHS Greater Glasgow and Clyde United Kingdom
- University of Cambridge United Kingdom
- Queen Mary University of London United Kingdom
- University of Queensland Australia
- University of London United Kingdom
IL28RA gene, genetic association, AUTOIMMUNITY, VARIANTS, Settore MED/03 - GENETICA MEDICA, Aminopeptidases, X chromosome, Major Histocompatibility Complex, single nucleotide polymorphism, Reference Values, genetic variability, Risk Assessment; Chromosome Mapping; Chromosomes, Human; Genetic Variation; Polymorphism, Single Nucleotide; Aminopeptidases; HLA-C Antigens; Humans; Major Histocompatibility Complex; Psoriasis; Europe; Genome-Wide Association Study; Reference Values; Genetic Predisposition to Disease; Chromosomes, Human, X, Chromosomes, Human, Disease, genetics, Reference Value, chromosome map, X, aminopeptidase, NCMLS 1: Infection and autoimmunity, article, TRAF3IP2 gene, risk assessment, Chromosome Mapping, psoriasis, Single Nucleotide, HLA C antigen, major histocompatibility complex, FAMILY, Europe, priority journal, DISEASES, nfkbia gene, ifih1 gene, Statistical-method, Human, ERAP1 protein, 570, gene locus, tyk2 gene, Aminopeptidase, 610, Gene interaction, HLA-C Antigens, Polymorphism, Single Nucleotide, Risk Assessment, Chromosomes, Minor Histocompatibility Antigens, 1311 Genetics, STATISTICAL-METHOD, 616, Humans, Psoriasis, controlled study, Genetic Predisposition to Disease, Polymorphism, Psoriasi, Chromosomes, Human, X, COMPLEX, HLA-C Antigen, gene interaction, REL gene, reference value, PATHWAYS, Genetic Variation, ERAP1 gene, human chromosome, major clinical study, GENE, genetic predisposition, SCAN, genetic susceptibility, RESPONSES, Genome-Wide Association Study
IL28RA gene, genetic association, AUTOIMMUNITY, VARIANTS, Settore MED/03 - GENETICA MEDICA, Aminopeptidases, X chromosome, Major Histocompatibility Complex, single nucleotide polymorphism, Reference Values, genetic variability, Risk Assessment; Chromosome Mapping; Chromosomes, Human; Genetic Variation; Polymorphism, Single Nucleotide; Aminopeptidases; HLA-C Antigens; Humans; Major Histocompatibility Complex; Psoriasis; Europe; Genome-Wide Association Study; Reference Values; Genetic Predisposition to Disease; Chromosomes, Human, X, Chromosomes, Human, Disease, genetics, Reference Value, chromosome map, X, aminopeptidase, NCMLS 1: Infection and autoimmunity, article, TRAF3IP2 gene, risk assessment, Chromosome Mapping, psoriasis, Single Nucleotide, HLA C antigen, major histocompatibility complex, FAMILY, Europe, priority journal, DISEASES, nfkbia gene, ifih1 gene, Statistical-method, Human, ERAP1 protein, 570, gene locus, tyk2 gene, Aminopeptidase, 610, Gene interaction, HLA-C Antigens, Polymorphism, Single Nucleotide, Risk Assessment, Chromosomes, Minor Histocompatibility Antigens, 1311 Genetics, STATISTICAL-METHOD, 616, Humans, Psoriasis, controlled study, Genetic Predisposition to Disease, Polymorphism, Psoriasi, Chromosomes, Human, X, COMPLEX, HLA-C Antigen, gene interaction, REL gene, reference value, PATHWAYS, Genetic Variation, ERAP1 gene, human chromosome, major clinical study, GENE, genetic predisposition, SCAN, genetic susceptibility, RESPONSES, Genome-Wide Association Study
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