4.8 Article

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

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NATURE GENETICS
卷 45, 期 7, 页码 808-+

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NATURE PUBLISHING GROUP
DOI: 10.1038/ng.2642

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资金

  1. Deutsche Forschungsgemeinschaft (DFG) [FR 2821/2-1]
  2. German Ministry of Education and Research (BMBF) through the National Genome Research Network (NGFN) [01GS 0818, 01GS 0812]
  3. PopGen biobank
  4. Heisenberg fellowship of the DFG [WE 2678/7-1]
  5. National Children's Research Centre, Dublin
  6. Wellcome Trust [090066/B/09/Z, 092530/Z/10/Z]
  7. DFG [BR1912/6-1]
  8. Else-Kroner-Fresenius-Stiftung [2010_EKES.32]
  9. US National Institutes of Health [1R01CA141743-01]
  10. University of Pittsburgh Genomics and Proteomics Core Laboratories for the Immunochip genotyping services
  11. Wellcome Trust Strategic Award [098439/Z/12/Z]
  12. General Program of National Natural Science Foundation of China [31171224]
  13. Program for New Century Excellent Talents in University [NCET-11-0889]
  14. Science and Technological Foundation of Anhui Province for Outstanding Youth [1108085J10]
  15. State Key Basic Research Program 973 of China [2012CB722404]
  16. Medical Research Council [G0700314] Funding Source: researchfish
  17. MRC [G0700314] Funding Source: UKRI

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Atopic dermatitis is a common inflammatory skin disease with a strong heritable component. Pathogenetic models consider keratinocyte differentiation defects and immune alterations as scaffolds(1), and recent data indicate a role for autoreactivity in at least a subgroup of patients(2). FLG (encoding filaggrin) has been identified as a major locus causing skin barrier deficiency(3). 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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