@article{5811fafcc7ab4635bff24ff53cbd4b85,
title = "Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis",
abstract = "Atopic disease, including atopic dermatitis (eczema), allergy and asthma, has increased in frequency in recent decades and now affects ~20% of the population in the developed world. Twin and family studies have shown that predisposition to atopic disease is highly heritable. Although most genetic studies have focused on immunological mechanisms, a primary epithelial barrier defect has been anticipated. Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Here we show that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis. These variants are carried by ~9% of people of European origin. These variants also show highly significant association with asthma occurring in the context of atopic dermatitis. This work establishes a key role for impaired skin barrier function in the development of atopic disease.",
author = "Palmer, {Colin N. A.} and Irvine, {Alan D.} and Ana Terron-Kwiatkowski and Yiwei Zhao and Haihui Liao and Lee, {Simon P.} and Goudie, {David R.} and Aileen Sandilands and Campbell, {Linda E.} and Smith, {Frances J. D.} and O'Regan, {Grainne M.} and Watson, {Rosemarie M.} and Cecil, {Jo E.} and Bale, {Sherri J.} and Compton, {John G.} and DiGiovanna, {John J.} and Philip Fleckman and Sue Lewis-Jones and Gehan Arseculeratne and Ann Sergeant and Munro, {Colin S.} and {El Houate}, Brahim and Ken McElreavey and Halkjaer, {Liselotte B.} and Hans Bisgaard and Somnath Mukhopadhyay and McLean, {W. H. Irwin}",
note = "dc.publisher: Nature Publishing Group Senior author responsible for overall strategy, funding, planning, analysis and writing of the first paper to show that mutations in the filaggrin gene are the major genetic susceptibility factor in atopic dermatitis and contribute to asthma driven by pre-existing eczema. This award-winning research has changed the landscape of eczema research. dc.description.sponsorship: Wellcome Trust Senior Research Fellowship Dystrophic Epidermolysis Bullosa Research Association Pachyonychia Congenita Project British Skin Foundation/National Eczema Society Biotechnology and Biological Sciences Research Council Award D13460 Scottish Enterprise Tayside and the Gannochy Trust Scottish Executive Genetic Health Initiative ",
year = "2006",
month = apr,
doi = "10.1038/ng1767",
language = "English",
volume = "38",
pages = "441--446",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Research",
number = "4",
}