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

Marenholz, Ingo and Esparza-Gordillo, Jorge and Rueschendorf, Franz and Bauerfeind, Anja and Strachan, David P. and Spycher, Ben D. and Baurecht, Hansjoerg and Margaritte-Jeannin, Patricia and Saaf, Annika and Kerkhof, Marjan and Ege, Markus and Baltic, Svetlana and Matheson, Melanie C. and Li, Jin and Michel, Sven and Ang, Wei Q. and McArdle, Wendy and Arnold, Andreas and Homuth, Georg and Demenais, Florence and Bouzigon, Emmanuelle and Soderhall, Cilla and Pershagen, Goran and de Jongste, Johan C. and Postma, Dirkje S. and Braun-Fahrlaender, Charlotte and Horak, Elisabeth and Ogorodova, Ludmila M. and Puzyrev, Valery P. and Bragina, Elena Yu and Hudson, Thomas J. and Morin, Charles and Duffy, David L. and Marks, Guy B. and Robertson, Colin F. and Montgomery, Grant W. and Musk, Bill and Thompson, Philip J. and Martin, Nicholas G. and James, Alan and Sleiman, Patrick and Toskala, Elina and Rodriguez, Elke and Foelster-Holst, Regina and Franke, Andre and Lieb, Wolfgang and Gieger, Christian and Heinzmann, Andrea and Rietschel, Ernst and Keil, Thomas and Cichon, Sven and Noethen, Markus M. and Pennell, Craig E. and Sly, Peter D. and Schmidt, Carsten O. and Matanovic, Anja and Schneider, Valentin and Heinig, Matthias and Huebner, Norbert and Holt, Patrick G. and Lau, Susanne and Kabesch, Michael and Weidinger, Stefan and Hakonarson, Hakon and Ferreira, Manuel A. R. and Laprise, Catherine and Freidin, Maxim B. and Genuneit, Jon and Koppelman, Gerard H. and Melen, Erik and Dizier, Marie-Helene and Henderson, A. John and Lee, Young Ae (2015) Meta-analysis identifies seven susceptibility loci involved in the atopic march. NATURE COMMUNICATIONS, 6: 8804. ISSN 2041-1723,

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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 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.

Item Type: Article
Uncontrolled Keywords: JUVENILE MYOCLONIC EPILEPSY; FOOD ALLERGY; FILAGGRIN MUTATIONS; BIRTH COHORT; HAY-FEVER; GENOMEWIDE ASSOCIATION; CHROMOSOME 11Q13; CHILDHOOD ASTHMA; DERMATITIS; RISK;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Kinder- und Jugendmedizin
Depositing User: Dr. Gernot Deinzer
Date Deposited: 06 May 2019 08:45
Last Modified: 06 May 2019 08:45
URI: https://pred.uni-regensburg.de/id/eprint/4518

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