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A common variant on chromosome 11q13 is associated with atopic dermatitis

Nature Genetics volume 41, pages 596–601 (2009)Cite this article

Abstract

We conducted a genome-wide association study in 939 individuals with atopic dermatitis and 975 controls as well as 270 complete nuclear families with two affected siblings. SNPs consistently associated with atopic dermatitis in both discovery sets were then investigated in two additional independent replication sets totalling 2,637 cases and 3,957 controls. Highly significant association was found with allele A of rs7927894 on chromosome 11q13.5, located 38 kb downstream of C11orf30 (Pcombined = 7.6 × 10−10). Approximately 13% of individuals of European origin are homozygous for rs7927894[A], and their risk of developing atopic dermatitis is 1.47 times that of noncarriers.

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Figure 1: Study design.
Figure 2: Association results and LD structure in the atopic dermatitis–associated region on 11q13.5.
Figure 3: Association results and LD structure in the epidermal differentiation complex (EDC) on 1q21.

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Acknowledgements

We thank all subjects with eczema, families and physicians for their participation. We thank I.v. Gwinner-Bühring, F. Kussebi, C. Ockeloen, T. Schilling and I. Schulz for subject evaluation. We are grateful to C. Flachmeier, S. Kolberg, M. Schwarz, I. Szangolies, S. Blachut, G. Born, S. Schmidt, C. v.d. Lancken, T. Henke, B. Fedders and T. Wesse for technical assistance, and to M. Wittig for database management. We thank L. Ghys and M. De Longueville (UCB Pharma) and the following EPAAC and ETAC investigators for providing case samples: O. Rybnícek (Brno, Czech Republic), J. Chládková, T. Chyba (Hradec Kralove, Czech Republic), F. Kopriva (Olomouc, Czech Republic), O. Škopková, V. Balcárek (Ostrava, Czech Republic), H. Honomichlova, P. Honomichlová-Houdkova, P. Honomichl (Plzen Lochotin, Czech Republic), M. Špicáková, S. Kynclova, V. Petru, A. Carbolova, K. Kopecká, P. Pohunek, T. Svobodova, V. Špicák, K. Kopecka, M.Maltulka (Praha, Czech Republic), M. Kaczmarski, B. Cudowska, J. Wasilewska, E. Matuszfewska (Bialystok, Poland), T. Malaczynska, B. Klajna-Kraluk (Gdansk, Poland), J. Sokalska, E. Masnica-Wasylkowska, I. Biegun-Awramineko, M. Chlon (Gliwice Poland), T. Latos, E. Pomaranska, G. Gaszczyk, B. Makuch, J. Stanisz, J. Bokiej (Karpacz, Poland), G. Lis, E. Cichocka-Jarosz, I. Glodzik, T. Szczerbinski (Kraków, Poland), D. Chlebna-Sokol, A. Stanczyk, J. Wlazlowski, I. Ligenza, B. Kamer, K. Pyziak, R. Pasowska, J. Zwaigzne-Raczynska (Lodz, Poland), A. Emeryk, H. Milanowska, G. Zywicka, M. Bartkowiak-Emeryk, E. Chojna (Lublin, Poland), A. Swiatly, A. Szczawinska-Poplonyk, M. Kulesza-Kazecka, J. Alkiewicz, A. Breborowicz (Poznan, Poland), R. Kurzawa, A. Wojcik, U. Jedrys-Klucjasz, E. Urbanek-Jozwik (Rabka Zdrój, Poland), L. Dymek, A. Dymek, A. Bozek (Strzelce opolskie, Poland), D. Chmielewska-Szewczyk, J. Lange, J. Peradzynska, M. Kulus, E. Najberg, E. Nowicka, A. Chrupek (Warszawa, Poland), A. Boznanski, E. Willak-Janc, A. Latkowska, E. Sikorska, M.T. Jarlinska (Wroclaw, Poland). The study was funded by the German Ministry of Education and Research (BMBF) through the Clinical Research Group for Allergy at Charité Berlin, the National Genome Research Network (NGFN), by the PopGen biobank and infrastructure support through the DFG cluster of excellence “Inflammation at Interfaces”. This work was supported by an EMBO long-term fellowship (522-2006) and by a Marie Curie EIF fellowship (039868) to J.E.G. N.N. was supported by grants from the German Research Council (DFG NO454/1-4, NO454/2-4, NO454/5-2, SFB704 TPA4) and BONFOR grants of the University of Bonn. S.W. was supported by research grants KKF-07/04 and KKF-27/05 of the University Hospital Rechts der Isar, Technische Universität München, a grant from the Wilhelm-Vaillant-Stiftung and a Heisenberg fellowship (DFG WE 2678/4-1) from the German Research Council. M.M. was supported by research grant VZFNM00064203.

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Author notes

  1. Jorge Esparza-Gordillo and Stephan Weidinger: These authors contributed equally to this work.

Authors and Affiliations

  1. Pediatric Pneumology and Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany

    Jorge Esparza-Gordillo, Ingo Marenholz, Florian Schulz, Tamara Kerscher, Ulrich Wahn & Young-Ae Lee

  2. Max-Delbrück-Centrum for Molecular Medicine (MDC), Berlin-Buch, Germany

    Jorge Esparza-Gordillo, Anja Bauerfeind, Franz Ruschendorf, Giannino Patone, Klaus Rohde, Ingo Marenholz, Florian Schulz, Tamara Kerscher, Norbert Hubner & Young-Ae Lee

  3. Department of Dermatology and Allergy, Technische Universität München, Munich, Germany

    Stephan Weidinger & Elke Rodriguez

  4. Division of Environmental Dermatology and Allergy, Helmholtz Zentrum Munich and ZAUM-Center for Allergy and Environment, Technische Universität München, Munich, Germany

    Stephan Weidinger, Hansjörg Baurecht & Elke Rodriguez

  5. Clinic for Dermatology, Venerology and Allergology, University Hospital Schleswig-Holstein, Kiel, Germany

    Regina Fölster-Holst

  6. Institute for Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany

    Stefan Schreiber, Andre Franke & Andreas Ruether

  7. POPGEN Biobank Project, Christian-Albrechts-University, Kiel, Germany

    Stefan Schreiber & Rainer Vogler

  8. Centre National de Génotypage, Evry, France

    Simon Heath

  9. Institute for Medical Statistics and Epidemiology IMSE, Technische Universität München, Munich, Germany

    Hansjörg Baurecht

  10. Department of Dermatology and Allergy, University of Bonn, Bonn, Germany

    Natalija Novak

  11. Department of Epidemiology, Helmholtz Zentrum Munich-German Research Center for Environmental Health, Neuherberg, Germany

    Thomas Illig

  12. Klinik fur Kinder- und Jugendmedizin, Technical University Dresden, Dresden, Germany

    Min-Ae Lee-Kirsch

  13. Department of Laboratory Diagnostics and Molecular Medicine, Pomeranian Medical University, Szczecin, Poland

    Andrzej Ciechanowicz

  14. Department of Clinical Allergology, Pomeranian, Pomeranian Medical University, Szczecin, Poland

    Michael Kurek

  15. Department of Biology and Medical Genetics, Charles University Prague, 2nd Medical School and Faculty, Hospital Motol, Prague, Czech Republic

    Tereza Piskackova & Milan Macek

Authors
  1. Jorge Esparza-Gordillo
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Contributions

J.E.G., Y.A.L., S.W., A.R. and N.H. designed the study. Y.A.L. directed the study. Y.A.L., J.E.G., S.W., R.F.-H., U.W., S.S., N.N., M.L.-K., A.C., M.K., T.P. and M.M. provided the case and control samples. J.E.G., S.W., A.R., G.P., A.F., R.V., H.B., T.I. and Y.A.L. contributed to biobanking and management of clinical data. J.E.G., G.P., I.M., F.S. and T.K. performed 500K array and Taqman genotyping. A.R. did the SNPlex genotyping; E.R. contributed to DNA extraction, biobanking and FLG genotyping of Munich samples. A.B., F.R., K.R., J.E.G., N.H. and Y.A.L. conducted all statistical analyses and interpreted the data. S.H. estimated population stratification in set 4. J.E.G. and Y.A.L. wrote the manuscript.

Corresponding author

Correspondence to Young-Ae Lee.

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Esparza-Gordillo, J., Weidinger, S., Fölster-Holst, R. et al. A common variant on chromosome 11q13 is associated with atopic dermatitis. Nat Genet 41, 596–601 (2009). https://doi.org/10.1038/ng.347

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