Back to Search
Start Over
Eight novel susceptibility loci and putative causal variants in atopic dermatitis.
- Source :
-
The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2021 Nov; Vol. 148 (5), pp. 1293-1306. Date of Electronic Publication: 2021 Jun 08. - Publication Year :
- 2021
-
Abstract
- Background: Atopic dermatitis (AD) is the most common allergic disease in the world. While genetic components play critical roles in its pathophysiology, a large proportion of its genetic background is still unexplored.<br />Objectives: This study sought to illuminate the genetic associations with AD using genome-wide association study (GWAS) and its downstream analyses.<br />Methods: This study conducted a GWAS for AD comprising 2,639 cases and 115,648 controls in the Japanese population, followed by a trans-ethnic meta-analysis with UK Biobank data and downstream analyses including partitioning heritability analysis by linkage disequilibrium score regression.<br />Results: This study identified 17 significant susceptibility loci, among which 4 loci-AFF1, ITGB8, EHMT1, and EGR2-were novel in the Japanese GWAS. The trans-ethnic meta-analysis revealed 4 additional novel loci, namely-ZBTB38,LOC105755953/LOC101928272, TRAF3, andIQGAP1. This study found a missense variant (R243W) with a deleterious functional effect in NLRP10 and a variant altering expression of CCDC80 via enhancer expression as highly likely causal variants. These 2 regions were Asian-specific, and these population-specific associations could be explained by the frequency of causal variants. The gene-based test showed SMAD4 as an additional novel significant locus. Downstream analyses revealed substantial overlap of GWAS significant signals in enhancers of skin cells and immune cells, especially CD4 T cells. A highly shared polygenic architecture of AD between Europeans and Asians was also found.<br />Conclusions: This study identified Japanese-specific loci and novel significant loci shared by different populations. Two putative causal variants were illuminated in Japanese-specific loci. Trans-ethnic analyses revealed strong heritability enrichment in immune-related pathways, and relevant cell types shared among populations.<br /> (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Case-Control Studies
DNA-Binding Proteins genetics
Female
Genetic Association Studies
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Immunity genetics
Japan epidemiology
Linkage Disequilibrium
Male
Polymorphism, Genetic
Transcriptional Elongation Factors genetics
Adaptor Proteins, Signal Transducing genetics
Apoptosis Regulatory Proteins genetics
Dermatitis, Atopic genetics
Genetic Loci genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1097-6825
- Volume :
- 148
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- The Journal of allergy and clinical immunology
- Publication Type :
- Academic Journal
- Accession number :
- 34116867
- Full Text :
- https://doi.org/10.1016/j.jaci.2021.04.019