title: Four genetic variants interact to confer susceptibility to atopic dermatitis in Chinese Han population.
abstract: Atopic dermatitis is a chronic inflammatory skin disease and is affected by environmental and genetic factors. Gene-gene/environment interactions are strongly believed to contribute to the genetic risk of common diseases. A number of gene-environment interactions of atopic dermatitis were performed. However, there are few comprehensive investigations on the gene-gene (or genetic variants) interactions for atopic dermatitis. We explored the association model of 6 single nucleotide polymorphisms (SNPs) which were most significant (P < 10E-05) in our previous genome wide association study (GWAS) for atopic dermatitis, and search for the possible genetic variant interactions based on the previous GWAS data using Generalized Multifactor Dimensionality Reduction and Plink 1.07 in the combined sample of 4,636 cases and 13,559 controls. The most significant associated evidence was observed under dominant model for SNPs rs3126085, rs12085366, and rs7701890, recessive model for SNP rs17173197, and additive model for SNPs rs2393903 and rs6010620. Three significant pair-way interactions were observed, including PRKAG2 and FLG SNPs (rs17173197 × rs3126085, P combined = 1.11E-15), PRKAG2 and TMEM232-SLC25A46 SNPs (rs17173197 × rs7701890, P combined = 2.22E-15), PRKAG2 and TNFRSF6B-ZGPAT SNPs (rs17173197 × rs6010620, P combined = 6.66E-16). Besides, a three-way significant interaction among PRKAG2, TMEM232-SLC25A46 and TNFRSF6B-ZGPAT SNPs (rs17173197 × rs7701890 × rs6010620, P combined = 5.99E-15) was observed in this study. These four genetic variant interactions confer susceptibility to atopic dermatitis, and highlight the genetic variant interactions in the etiology of atopic dermatitis in Chinese Han population.
authors.affiliation: Institute and Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China.
authors.forename: Changbing
authors.initials: C
authors.lastname: Shen
authors.forename: Longdan
authors.initials: L
authors.lastname: Liu
authors.forename: Zengqiong
authors.initials: Z
authors.lastname: Jiang
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zheng
authors.forename: Li
authors.initials: L
authors.lastname: Meng
authors.forename: Xianyong
authors.initials: X
authors.lastname: Yin
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.forename: Yujun
authors.initials: Y
authors.lastname: Sheng
authors.forename: Jingping
authors.initials: J
authors.lastname: Gao
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Fusheng
authors.initials: F
authors.lastname: Zhou
authors.forename: Fengli
authors.initials: F
authors.lastname: Xiao
authors.forename: Liangdan
authors.initials: L
authors.lastname: Sun
authors.forename: Yong
authors.initials: Y
authors.lastname: Cui
authors.forename: Sen
authors.initials: S
authors.lastname: Yang
authors.forename: Xianbo
authors.initials: X
authors.lastname: Zuo
authors.forename: Xuejun
authors.initials: X
authors.lastname: Zhang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics; D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002681:China; D003876:Dermatitis, Atopic / Q000208:ethnology / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D000091344:Filaggrin Proteins; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D007223:Infant; D007381:Intermediate Filament Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics; D028061:Phosphate Transport Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000235:genetics; D055815:Young Adult
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D024101:Mitochondrial Proteins; D028061:Phosphate Transport Proteins; D053323:Receptors, Tumor Necrosis Factor, Member 6b; C584459:SLC25A46 protein, human; C505911:TNFRSF6B protein, human; C526223:PRKAG2 protein, human; D055372:AMP-Activated Protein Kinases