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

Author

Listed:
  • Ingo Marenholz

    (Max-Delbrück-Center (MDC) for Molecular Medicine
    Clinic for Pediatric Allergy, Experimental and Clinical Research Center, Charité University Medical Center)

  • Jorge Esparza-Gordillo

    (Max-Delbrück-Center (MDC) for Molecular Medicine
    Clinic for Pediatric Allergy, Experimental and Clinical Research Center, Charité University Medical Center)

  • Franz Rüschendorf

    (Max-Delbrück-Center (MDC) for Molecular Medicine)

  • Anja Bauerfeind

    (Max-Delbrück-Center (MDC) for Molecular Medicine)

  • David P. Strachan

    (Population Health Research Institute, St George’s, University of London)

  • Ben D. Spycher

    (Institute of Social and Preventive Medicine, University of Bern)

  • Hansjörg Baurecht

    (Allergology, and Venerology, University Hospital Schleswig-Holstein, Campus Kiel)

  • Patricia Margaritte-Jeannin

    (Inserm, UMR-946
    Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d’Hématologie)

  • Annika Sääf

    (Institute of Environmental Medicine, Karolinska Institutet)

  • Marjan Kerkhof

    (University of Groningen, University Medical Center Groningen, GRIAC Research Institute)

  • Markus Ege

    (Dr von Hauner Children’s Hospital, Ludwig Maximilians University Munich, Member of the German Center for Lung Research (DZL))

  • Svetlana Baltic

    (Lung Institute of Western Australia, University of Western Australia)

  • Melanie C. Matheson

    (Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne)

  • Jin Li

    (Center for Applied Genomics, The Children’s Hospital of Philadelphia)

  • Sven Michel

    (University Children`s Hospital Regensburg (KUNO))

  • Wei Q. Ang

    (School of Women and Infant’s Health, University of Western Australia)

  • Wendy McArdle

    (School of Social and Community Medicine, University of Bristol)

  • Andreas Arnold

    (Clinic and Polyclinic of Dermatology, University Medicine Greifswald)

  • Georg Homuth

    (Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt-University Greifswald)

  • Florence Demenais

    (Inserm, UMR-946
    Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d’Hématologie)

  • Emmanuelle Bouzigon

    (Inserm, UMR-946
    Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d’Hématologie)

  • Cilla Söderhäll

    (and Center for Innovative Medicine (CIMED), Karolinska Institutet)

  • Göran Pershagen

    (Institute of Environmental Medicine, Karolinska Institutet)

  • Johan C. de Jongste

    (Pediatric Chest Center, Erasmus University Medical Center)

  • Dirkje S. Postma

    (University of Groningen, University Medical Center Groningen)

  • Charlotte Braun-Fahrländer

    (Swiss Tropical and Public Health Institute and the University of Basel)

  • Elisabeth Horak

    (Innsbruck Medical University)

  • Ludmila M. Ogorodova

    (Siberian State Medical University)

  • Valery P. Puzyrev

    (Siberian State Medical University
    Research Institute of Medical Genetics)

  • Elena Yu Bragina

    (Research Institute of Medical Genetics)

  • 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

    (Woolcock Institute of Medical Research, University of Sydney)

  • Colin F. Robertson

    (Murdoch Children’s Research Institute)

  • Grant W. Montgomery

    (QIMR Berghofer Medical Research Institute)

  • Bill Musk

    (Busselton Population Medical Research Foundation, Sir Charles Gairdner Hospital)

  • Philip J. Thompson

    (Lung Institute of Western Australia, University of Western Australia)

  • Nicholas G. Martin

    (QIMR Berghofer Medical Research Institute)

  • Alan James

    (Busselton Population Medical Research Foundation, Sir Charles Gairdner Hospital)

  • Patrick Sleiman

    (Center for Applied Genomics, The Children’s Hospital of Philadelphia
    Perelman School of Medicine, University of Pennsylvania)

  • Elina Toskala

    (Temple University, School of Medicine)

  • Elke Rodriguez

    (Allergology, and Venerology, University Hospital Schleswig-Holstein, Campus Kiel)

  • Regina Fölster-Holst

    (Allergology, and Venerology, University Hospital Schleswig-Holstein, Campus Kiel)

  • Andre Franke

    (Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel)

  • Wolfgang Lieb

    (Institute of Epidemiology, Christian-Albrechts-University of Kiel)

  • Christian Gieger

    (Research Unit of Molecular Epidemiology and Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Andrea Heinzmann

    (University Children’s Hospital, Albert Ludwigs University)

  • Ernst Rietschel

    (University Children’s Hospital, University of Cologne)

  • Thomas Keil

    (Institute of Social Medicine, Epidemiology and Health Economics, Charité University Medical Center
    Institute for Clinical Epidemiology and Biometry, University of Würzburg)

  • Sven Cichon

    (Institute of Human Genetics, University of Bonn
    Life & Brain Center, University of Bonn
    University of Basel
    Institute of Neuroscience and Medicine (INM-1), Structural and Functional Organisation of the Brain, Genomic Imaging, Research Centre Jülich)

  • Markus M. Nöthen

    (Institute of Human Genetics, University of Bonn
    Life & Brain Center, University of Bonn)

  • Craig E. Pennell

    (School of Women and Infant’s Health, University of Western Australia)

  • Peter D. Sly

    (Queensland Children’s Medical Research Institute, University of Queensland)

  • Carsten O. Schmidt

    (Institute for Community Medicine, Study of Health in Pomerania/KEF, University Medicine Greifswald)

  • Anja Matanovic

    (Max-Delbrück-Center (MDC) for Molecular Medicine
    Clinic for Pediatric Allergy, Experimental and Clinical Research Center, Charité University Medical Center)

  • Valentin Schneider

    (Max-Delbrück-Center (MDC) for Molecular Medicine)

  • Matthias Heinig

    (Max-Delbrück-Center (MDC) for Molecular Medicine
    Max Planck Institute for Molecular Genetics)

  • Norbert Hübner

    (Max-Delbrück-Center (MDC) for Molecular Medicine)

  • Patrick G. Holt

    (Queensland Children’s Medical Research Institute, University of Queensland
    Telethon Kids Institute, University of Western Australia)

  • Susanne Lau

    (Charité University Medical Center)

  • Michael Kabesch

    (University Children`s Hospital Regensburg (KUNO))

  • Stefan Weidinger

    (Allergology, and Venerology, University Hospital Schleswig-Holstein, Campus Kiel)

  • Hakon Hakonarson

    (Center for Applied Genomics, The Children’s Hospital of Philadelphia
    Perelman School of Medicine, University of Pennsylvania)

  • Manuel A. R. Ferreira

    (QIMR Berghofer Medical Research Institute)

  • Catherine Laprise

    (Université du Québec à Chicoutimi)

  • Maxim B. Freidin

    (Research Institute of Medical Genetics)

  • Jon Genuneit

    (Institute of Epidemiology and Medical Biometry, Ulm University)

  • Gerard H. Koppelman

    (University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital and GRIAC Research Institute)

  • Erik Melén

    (Institute of Environmental Medicine, Karolinska Institutet
    Sachs’ Children’s Hospital)

  • Marie- Hélène Dizier

    (Inserm, UMR-946
    Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d’Hématologie)

  • A John Henderson

    (School of Social and Community Medicine, University of Bristol)

  • Young Ae Lee

    (Max-Delbrück-Center (MDC) for Molecular Medicine
    Clinic for Pediatric Allergy, Experimental and Clinical Research Center, Charité University Medical Center)

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.

Suggested Citation

  • Ingo Marenholz & Jorge Esparza-Gordillo & Franz Rüschendorf & Anja Bauerfeind & David P. Strachan & Ben D. Spycher & Hansjörg Baurecht & Patricia Margaritte-Jeannin & Annika Sääf & Marjan Kerkhof & Ma, 2015. "Meta-analysis identifies seven susceptibility loci involved in the atopic march," Nature Communications, Nature, vol. 6(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9804
    DOI: 10.1038/ncomms9804
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