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

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 in...

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Published in:	Nature communications Vol. 6; no. 1; p. 8804
Main Authors:	Marenholz, Ingo, Esparza-Gordillo, Jorge, Rüschendorf, Franz, Bauerfeind, Anja, Strachan, David P., Spycher, Ben D., Baurecht, Hansjörg, Margaritte-Jeannin, Patricia, Sääf, Annika, Kerkhof, Marjan, Ege, Markus, Baltic, Svetlana, Matheson, Melanie C., Li, Jin, Michel, Sven, Ang, Wei Q., McArdle, Wendy, Arnold, Andreas, Homuth, Georg, Demenais, Florence, Bouzigon, Emmanuelle, Söderhäll, Cilla, Pershagen, Göran, de Jongste, Johan C., Postma, Dirkje S., Braun-Fahrländer, Charlotte, Horak, Elisabeth, Ogorodova, Ludmila M., Puzyrev, Valery P., Bragina, Elena Yu, Hudson, Thomas J., Morin, Charles, Duffy, David L., Marks, Guy B., Robertson, Colin F., Montgomery, Grant W., Musk, Bill, Thompson, Philip J., Martin, Nicholas G., James, Alan, Sleiman, Patrick, Toskala, Elina, Rodriguez, Elke, Fölster-Holst, Regina, Franke, Andre, Lieb, Wolfgang, Gieger, Christian, Heinzmann, Andrea, Rietschel, Ernst, Keil, Thomas, Cichon, Sven, Nöthen, Markus M., Pennell, Craig E., Sly, Peter D., Schmidt, Carsten O., Matanovic, Anja, Schneider, Valentin, Heinig, Matthias, Hübner, Norbert, Holt, Patrick G., Lau, Susanne, Kabesch, Michael, Weidinger, Stefan, Hakonarson, Hakon, Ferreira, Manuel A. R., Laprise, Catherine, Freidin, Maxim B., Genuneit, Jon, Koppelman, Gerard H., Melén, Erik, Dizier, Marie- Hélène, Henderson, A John, Lee, Young Ae
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 06.11.2015 Nature Publishing Group Nature Pub. Group
Subjects:	631/208/2489/144 631/250/249/2510/31 692/1807/1812 692/420 Adaptor Proteins, Vesicular Transport - genetics Adolescent Adult Allergic diseases Amino Acid Transport Systems, Neutral - genetics Asthma Asthma - genetics Atopy Calcium-Binding Proteins - genetics Carrier Proteins - genetics Child Child, Preschool Children Chromosome 12 Chromosome 6 Dermatitis, Atopic - genetics Disease Progression DNA-Binding Proteins - genetics Eczema Female Filaggrin Proteins Genetic Predisposition to Disease Genome-wide association studies Genome-Wide Association Study Genomes Genotype Humanities and Social Sciences Humans Ikaros Transcription Factor - genetics Interleukin 4 Interleukin-4 - genetics Kinesins - genetics Life Sciences Loci Logistic Models Male Membrane Proteins - genetics Meta-analysis Middle Aged multidisciplinary Neoplasm Proteins - genetics Nerve Tissue Proteins - genetics Nuclear Proteins - genetics Phenotype Phenotypes Polymorphism, Single Nucleotide Receptor, Fibroblast Growth Factor, Type 1 - genetics Repressor Proteins - genetics Science Science (multidisciplinary) Skin diseases Statistics Transcription Factors - genetics Young Adult
ISSN:	2041-1723, 2041-1723
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Summary:	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. The development of asthma following eczema is known as the atopic march. Here the authors conduct a GWAS on affected children and identify two novel loci associated with the disease phenotype.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 content type line 14 ObjectType-Feature-3 ObjectType-Evidence Based Healthcare-1 ObjectType-Article-1 ObjectType-Feature-2 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/ncomms9804