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


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.

SUBMITTER: Marenholz I 

PROVIDER: S-EPMC4667629 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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

Marenholz Ingo I   Esparza-Gordillo Jorge J   Rüschendorf Franz F   Bauerfeind Anja A   Strachan David P DP   Spycher Ben D BD   Baurecht Hansjörg H   Margaritte-Jeannin Patricia P   Sääf Annika A   Kerkhof Marjan M   Ege Markus M   Baltic Svetlana S   Matheson Melanie C MC   Li Jin J   Michel Sven S   Ang Wei Q WQ   McArdle Wendy W   Arnold Andreas A   Homuth Georg G   Demenais Florence F   Bouzigon Emmanuelle E   Söderhäll Cilla C   Pershagen Göran G   de Jongste Johan C JC   Postma Dirkje S DS   Braun-Fahrländer Charlotte C   Horak Elisabeth E   Ogorodova Ludmila M LM   Puzyrev Valery P VP   Bragina Elena Yu EY   Hudson Thomas J TJ   Morin Charles C   Duffy David L DL   Marks Guy B GB   Robertson Colin F CF   Montgomery Grant W GW   Musk Bill B   Thompson Philip J PJ   Martin Nicholas G NG   James Alan A   Sleiman Patrick P   Toskala Elina E   Rodriguez Elke E   Fölster-Holst Regina R   Franke Andre A   Lieb Wolfgang W   Gieger Christian C   Heinzmann Andrea A   Rietschel Ernst E   Keil Thomas T   Cichon Sven S   Nöthen Markus M MM   Pennell Craig E CE   Sly Peter D PD   Schmidt Carsten O CO   Matanovic Anja A   Schneider Valentin V   Heinig Matthias M   Hübner Norbert N   Holt Patrick G PG   Lau Susanne S   Kabesch Michael M   Weidinger Stefan S   Hakonarson Hakon H   Ferreira Manuel A R MAR   Laprise Catherine C   Freidin Maxim B MB   Genuneit Jon J   Koppelman Gerard H GH   Melén Erik E   Dizier Marie-Hélène MH   Henderson A John AJ   Lee Young Ae YA  

Nature communications 20151106


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  ...[more]

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