High-density genotyping study identifies four new susceptibility loci for atopic dermatitis.

Publisher: Nature Pub. Co Country of Publication: United States NLM ID: 9216904 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-1718 (Electronic) Linking ISSN: 10614036 NLM ISO Abbreviation: Nat Genet Subsets: MEDLINE

Original Publication: New York, NY : Nature Pub. Co., c1992-

Genetic Loci*/genetics ; Genetic Predisposition to Disease*/ethnology ; Genetic Predisposition to Disease*/genetics; Dermatitis, Atopic/*genetics; Asian People/genetics ; Case-Control Studies ; Dermatitis, Atopic/ethnology ; Female ; Filaggrin Proteins ; Genome-Wide Association Study ; Genotyping Techniques ; Germany ; High-Throughput Nucleotide Sequencing ; Humans ; Intermediate Filament Proteins/genetics ; Japan ; Male ; Meta-Analysis as Topic ; Polymorphism, Single Nucleotide ; White People/genetics

Atopic dermatitis is a common inflammatory skin disease with a strong heritable component. Pathogenetic models consider keratinocyte differentiation defects and immune alterations as scaffolds, and recent data indicate a role for autoreactivity in at least a subgroup of patients. FLG (encoding filaggrin) has been identified as a major locus causing skin barrier deficiency. To better define risk variants and identify additional susceptibility loci, we densely genotyped 2,425 German individuals with atopic dermatitis (cases) and 5,449 controls using the Immunochip array followed by replication in 7,196 cases and 15,480 controls from Germany, Ireland, Japan and China. We identified four new susceptibility loci for atopic dermatitis and replicated previous associations. This brings the number of atopic dermatitis risk loci reported in individuals of European ancestry to 11. We estimate that these susceptibility loci together account for 14.4% of the heritability for atopic dermatitis.

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R01 CA141743 United States CA NCI NIH HHS; G0700314 United Kingdom MRC_ Medical Research Council; 1R01CA141743-01 United States CA NCI NIH HHS; 090066/B/09/Z United Kingdom WT_ Wellcome Trust; R01 AR050511 United States AR NIAMS NIH HHS; 092530/Z/10/Z United Kingdom WT_ Wellcome Trust; R01 AR063611 United States AR NIAMS NIH HHS; 098439/Z/12/Z United Kingdom WT_ Wellcome Trust; RC1 AR058315 United States AR NIAMS NIH HHS; 090066 United Kingdom WT_ Wellcome Trust; 098439 United Kingdom WT_ Wellcome Trust; UL1 TR000005 United States TR NCATS NIH HHS; 092530 United Kingdom WT_ Wellcome Trust; United Kingdom WT_ Wellcome Trust

Indexing Agency: NLM Local ID #: EMS54941.

0 (FLG protein, human)
0 (Filaggrin Proteins)
0 (Intermediate Filament Proteins)

Date Created: 20130604 Date Completed: 20130910 Latest Revision: 20230620

20231215

PMC3797441

10.1038/ng.2642

23727859