Abstract
Atopic dermatitis (AD) is a common inflammatory skin disease with high heritability. Two susceptibility loci have been confirmed in our previous AD genome-wide association study (GWAS). To look for additional genetic factors in Chinese Han ethnicity, we performed a large-scale GWAS follow-up study. Forty-nine top single nucleotide polymorphisms (SNPs) that had never been reported previously were genotyped using Sequenom Massarray system in an independent cohort, which consist of northern Chinese (1634 cases and 1263 controls) and southern Chinese (2985 cases and 9526 controls). Association analyses were performed using PLINK 2 software. Three SNPs in northern and ten SNPs in southern were found exhibiting association evidence with AD (P < 0.05). Finally, SNP rs224108 on 10q21.2 showed high significance for AD in joint analysis of GWAS and replication study (Pmeta = 4.55 × 10−9, OR = 1.21), and was confirmed as an independent genetic marker by Linkage disequilibrium calculation and conditional logistic regression analysis. Bioinformatics analysis strongly suggested that rs224108 may have the potential to alter the target gene expression through non-coding epigenetic regulation effects. Meanwhile, SNP rs11150780 on 17q25.3 was also found suggestive association with AD (Pmeta = 7.64 × 10−7, OR = 1.18). Our findings confirmed a novel susceptibility signal on 10q21.2 for AD in Chinese Han population and advanced the understanding of the genetic contribution to AD.
Highlights
Atopic dermatitis (AD) is a chronic inflammatory skin disease and characterized by intense itching and recurrent eczematous lesions
Since the study was based on initial genome-wide association study (GWAS), statistical threshold of joint P value for significant associated single nucleotide polymorphisms (SNPs) was set at 5 × 10−8
When the genotypic data from the primary GWAS and the replication stage were combined by meta-analysis, we found that the significance of association at rs224108 exceeded the genome-wide threshold (Pmeta = 4.55 × 10−9, odds ratios (ORs) = 1.21), and another SNP rs11150780 showed suggestive association with AD (Pmeta = 7.64 × 10−7, OR = 1.18) (Table 2)
Summary
Atopic dermatitis (AD) is a chronic inflammatory skin disease and characterized by intense itching and recurrent eczematous lesions. Several recent genome-wide association studies (GWASs) in multiple ethnic groups have identified 38 susceptibility loci (Esparza-Gordillo et al, 2009, 2013; Paternoster et al, 2011, 2015; Sun et al, 2011; Hirota et al, 2012; Ellinghaus et al, 2013; Weidinger et al, 2013; Kim et al, 2015; Marenholz et al, 2015; Schaarschmidt et al, 2015), providing vital clues for understanding the underlying genetic basis of AD Most of these loci were shown to be associated with skin epithelial function and innate/adaptive immune response, highlighting the two major pathogenetic pathways of AD.
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