GWAS Follow-up Study Discovers a Novel Genetic Signal on 10q21.2 for Atopic Dermatitis in Chinese Han Population

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.

Uniting biobank resources reveals novel genetic pathways modulating susceptibility for atopic dermatitis

“…RegulomeDB 16 annotation provided evidence for a possible regulatory mechanism for the detected association that may involve altered binding of early growth response 2 (Table II), a transcription factor that has been previously implicated in AD susceptibility in the Chinese Han population. 17 Of note, there was a suggestive association at 6q23.3 near genes IL-22 receptor subunit alpha-1 and IFN-g receptor 1 (P 5 2.77 3 10 27 ), providing additional evidence that IL-22 and/or IFN-g may be involved in modulating AD risk.…”

Validation of Susceptibility Loci for Vitiligo Identified by GWAS in the Chinese Han Population

“…After the concentration and purity were measured using a spectrophotometer, the 26 SNPs were genotyped using the Sequenom MassARRAY platform (Sequenom, San Diego, CA, United States). The procedures used for genotyping were presented in a previous study ( Cai et al, 2019 ).…”