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

Ingo Marenholz(Max Delbrück Center), Jorge Esparza-Gordillo(Max Delbrück Center), Franz Rüschendorf(Max Delbrück Center), Anja Bauerfeind(Max Delbrück Center), David P. Strachan(St George's, University of London), Ben D. Spycher(University of Bern), Hansjörg Baurecht(University Hospital Schleswig-Holstein), Patricia Margaritte‐Jeannin(Inserm), Annika Sääf(Karolinska Institutet), Marjan Kerkhof(University Medical Center Groningen), Markus Ege(German Center for Lung Research), Svetlana Baltic(The University of Western Australia), Melanie C. Matheson(The University of Melbourne), Jin Li(Children's Hospital of Philadelphia), Sven Michel(University Hospital Regensburg), Wei Ang(The University of Western Australia), Wendy L. McArdle(University of Bristol), Andreas Arnold(Universitätsmedizin Greifswald), Georg Homuth(Universität Greifswald), Florence Démenais(Inserm), Emmanuelle Bouzigon(Inserm), Cilla Söderhäll(Karolinska Institutet), Göran Pershagen(Karolinska Institutet), Johan C. de Jongste(Erasmus MC), Dirkje S. Postma(University Medical Center Groningen), Charlotte Braun‐Fahrländer(Swiss Tropical and Public Health Institute), Elisabeth Horak(Innsbruck Medical University), Л. М. Огородова(Siberian State Medical University), В. П. Пузырев(Siberian State Medical University), E. Yu. Bragina(Research Institute of Medical Genetics of Russian Academy of Medical Sciences), Thomas J. Hudson(Ontario Institute for Cancer Research), Charles Morin(Centre de Santé et de Services Sociaux de Chicoutimi), David L. Duffy(QIMR Berghofer Medical Research Institute), Guy B. Marks(The University of Sydney), Colin Robertson(Murdoch Children's Research Institute), Grant W. Montgomery(QIMR Berghofer Medical Research Institute), Bill Musk(Sir Charles Gairdner Hospital), Philip J. Thompson(The University of Western Australia), Nicholas G. Martin(QIMR Berghofer Medical Research Institute), Alan James(Sir Charles Gairdner Hospital), Patrick Sleiman(Children's Hospital of Philadelphia), Elina Toskala(Temple University), Elke Rodríguez(University Hospital Schleswig-Holstein), Regina Fölster‐Holst(University Hospital Schleswig-Holstein), André Franke(Christian-Albrechts-Universität zu Kiel), Wolfgang Lieb(Christian-Albrechts-Universität zu Kiel), Christian Gieger(Helmholtz Zentrum München), Andrea Heinzmann, Ernst Rietschel(University of Cologne), Thomas Keil(University of Würzburg), Sven Cichon(University of Bonn), Markus M. Nöthen(University of Bonn), Craig E. Pennell(The University of Western Australia), Peter D. Sly(The University of Queensland), Carsten Oliver Schmidt(Universitätsmedizin Greifswald), Anja Matanovic(Max Delbrück Center), Valentin Schneider-Lunitz(Max Delbrück Center), Matthias Heinig(Max Delbrück Center), Norbert Hübner(Max Delbrück Center), Patrick G. Holt(The University of Queensland), Susanne Lau(Charité - Universitätsmedizin Berlin), Michael Kabesch(University Hospital Regensburg), Stefan Weidinger(University Hospital Schleswig-Holstein), Håkon Håkonarson(Children's Hospital of Philadelphia), Manuel A. R. Ferreira(QIMR Berghofer Medical Research Institute), Catherine Laprise(Université du Québec à Chicoutimi), Maxim B. Freidin(Research Institute of Medical Genetics of Russian Academy of Medical Sciences), Jon Genuneit(Universität Ulm), Gerard H. Koppelman(University Medical Center Groningen), Erik Melén(Karolinska Institutet), Marie‐Hélène Dizier(Inserm), A. John Henderson(University of Bristol), Young Ae Lee(Max Delbrück Center)
Nature Communications
November 6, 2015
10.1038/ncomms9804
Cited by 174Open Access
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Abstract

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; P=2.1 × 10(-8)) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P=5.3 × 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.

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