A genome-wide association study of atopic dermatitis identifies loci with overlapping effects on asthma and psoriasis

Abstract

Atopic dermatitis (AD) is the most common dermatological disease of childhood. Many children with AD have asthma and AD shares regions of genetic linkage with psoriasis, another chronic inflammatory skin disease. We present here a genome-wide association study (GWAS) of childhood-onset AD in 1563 European cases with known asthma status and 4054 European controls. Using Illumina genotyping followed by imputation, we generated 268 034 consensus genotypes and in excess of 2 million single nucleotide polymorphisms (SNPs) for analysis. Association signals were assessed for replication in a second panel of 2286 European cases and 3160 European controls. Four loci achieved genome-wide significance for AD and replicated consistently across all cohorts. These included the epidermal differentiation complex (EDC) on chromosome 1, the genomic region proximal to LRRC32 on chromosome 11, the RAD50/IL13 locus on chromosome 5 and the major histocompatibility complex (MHC) on chromosome 6; reflecting action of classical HLA alleles. We observed variation in the contribution towards co-morbid asthma for these regions of association. We further explored the genetic relationship between AD, asthma and psoriasis by examining previously identified susceptibility SNPs for these diseases. We found considerable overlap between AD and psoriasis together with variable coincidence between allergic rhinitis (AR) and asthma. Our results indicate that the pathogenesis of AD incorporates immune and epidermal barrier defects with combinations of specific and overlapping effects at individual loci.

Association between psoriasis and asthma risk: A meta-analysis

“…9,12,27 There is evidence that psoriasis may be associated with asthma risk. 8,21,28 A longitudinal study by Fang et al 8 indicated that a psoriasis population has an increased risk of developing asthma. Asthma is a chronic inflammatory disorder of the airway that is caused by multiple factors that involve environmental, genetic, and immunologic factors.…”

“…32 Further studies indicate that genetic risk loci might be partially overlapped between asthma and psoriasis. 11,28,33 Interestingly, studies also found that psoriasis is associated with an increased risk of migraine and chronic obstructive pulmonary disease. 34,35 TNF-␣ has been shown to promote the pathogenesis of migraine by sensitization of meningeal nociceptors and peripheral nerve endings through activation of the p38 mitogen-activated protein kinases pathway, 36 and elevation of TNF-␣, interferon ␥, and IL-23 in patients with psoriasis could lead to an increased risk of chronic obstructive pulmonary disease by causing pulmonary inflammatory responses.…”

Association between atopic dermatitis-related single nucleotide polymorphisms rs4722404 and psoriasis vulgaris in a southern Chinese cohort

“…GWA studies have identified a strong relationship between the common SNP rs4722404 in CARD11 and AD (Hirota et al, 2012;Weidinger et al, 2013). Genetic evidence has demonstrated a higher level of genomic similarities between AD and psoriasis (Weidinger et al, 2013).…”

“…Genetic evidence has demonstrated a higher level of genomic similarities between AD and psoriasis (Weidinger et al, 2013). However, the effect of the SNP rs4722404 on the risk and clinical features of psoriasis, as well as the biological mechanism underlying this role, remain unclear.…”

“…Genome-wide association (GWA) studies have also demonstrated a high degree of genetic overlap between these two common skin disorders (Baurecht et al, 2015). GWA studies have identified an association between the single nucleotide polymorphism (SNP) rs4722404, in the caspase recruitment domain family member 11 gene (CARD11) on chromosome 7, and AD (Hirota et al, 2012;Weidinger et al, 2013). The identification of shared genetic components highlights the key molecular pathways involved in chronic inflammatory skin diseases; therefore, we further explored the association between the SNP rs4722404 and psoriasis vulgaris (PsV) in a Chinese Cohort.…”