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

Ingo Marenholz, Jorge Esparza-Gordillo, Franz Rüschendorf, Anja Bauerfeind, David P. Strachan, Ben D. Spycher, Hansjörg Baurecht, Patricia Margaritte-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. Pennell, 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 and Young Ae Lee ()
Additional contact information
Ingo Marenholz: Max-Delbrück-Center (MDC) for Molecular Medicine
Jorge Esparza-Gordillo: Max-Delbrück-Center (MDC) for Molecular Medicine
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
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
Emmanuelle Bouzigon: Inserm, UMR-946
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
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
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
Sven Cichon: Institute of Human Genetics, University of Bonn
Markus M. Nöthen: Institute of Human Genetics, 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
Valentin Schneider: Max-Delbrück-Center (MDC) for Molecular Medicine
Matthias Heinig: Max-Delbrück-Center (MDC) for Molecular Medicine
Norbert Hübner: Max-Delbrück-Center (MDC) for Molecular Medicine
Patrick G. Holt: Queensland Children’s Medical Research Institute, University of Queensland
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
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
Marie- Hélène Dizier: Inserm, UMR-946
A John Henderson: School of Social and Community Medicine, University of Bristol
Young Ae Lee: Max-Delbrück-Center (MDC) for Molecular Medicine

Nature Communications, 2015, vol. 6, issue 1, 1-8

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms9804

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