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Meta-analysis identifies seven susceptibility loci involved in the atopic march

Please always quote using this URN: urn:nbn:de:bvb:20-opus-139835
  • Eczema often precedes the development of asthma in a disease course called the 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; PEczema often precedes the development of asthma in a disease course called the 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P = 2.1 x 10(-8)) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P = 5.3 x 10(-9)). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.show moreshow less

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Author: Ingo Marenholz, Jorge Esparza-Gordillo, Franz Rüschendorf, Anja Bauerfeind, David P. Strachan, Ben D. Spycher, Hansjörg Baurecht, Patricia Magaritte-Jeannin, Annika Sääf, Marjan Kerkhof, Markus Ege, Svetlana Baltic, Melanie C. Matheson, Jin Li, Sven Michel, Wei Q. Ang, Wendy McArdle, Andreas Arnold, Georg Homuth, Florence Demenais, Emmanuelle Bouzigon, Cilla Söderhäll, Göran Pershagen, Johan C. de Jongste, Dirkje S. Postma, Charlotte Braun-Fahrländer, Elisabeth Horak, Ludmila M. Ogorodova, Valery P. Puzyrev, Elena Yu Bragina, Thomas J. Hudson, Charles Morin, David L. Duffy, Guy B. Marks, Colin F. Robertson, Grant W. Montgomery, Bill Musk, Philip J. Thompson, Nicholas G. Martin, Alan James, Patrick Sleiman, Elina Toskala, Elke Rodriguez, Regina Fölster-Holst, Andre Franke, Wolfgang Lieb, Christian Gieger, Andrea Heinzmann, Ernst Rietschel, Thomas Keil, Sven Cichon, Markus M. Nöthen, Craig E. Pennel, Peter D. Sly, Carsten O. Schmidt, Anja Matanovic, Valentin Schneider, Matthias Heinig, Norbert Hübner, Patrick G. Holt, Susanne Lau, Michael Kabesch, Stefan Weidinger, Hakon Hakonarson, Manuel A. R. Ferreira, Catherine Laprise, Maxim B. Freidin, Jon Genuneit, Gerard H. Koppelman, Erik Melén, Marie-Hélène Dizier, A. John Henderson, Young Ae Lee
URN:urn:nbn:de:bvb:20-opus-139835
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Klinische Epidemiologie und Biometrie
Language:English
Parent Title (English):Nature Communications
Year of Completion:2015
Volume:6
Issue:8804
Source:Nature Communications 6:8804 doi: 10.1038/ncomms9804 (2015).
DOI:https://doi.org/10.1038/ncomms9804
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:birth cohort; childhood asthma; chromosome 11Q13; dermatitis; filaggrin mutations; food allergy; genomewide association; hay fever; juvenile myoclonic epilepsy; risk
Release Date:2016/10/27
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung