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
Max-Delbrück-Center (MDC) for Molecular Medicine, Berlin, Germany.
Clinic for Pediatric Allergy, Experimental and Clinical Research Center, Charité University Medical Center, Berlin, Germany.
Nat Commun. 2015 Nov 6;6:8804. doi: 10.1038/ncomms9804.
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.
在一种称为“特应性进程”的疾病过程中，湿疹通常先于哮喘出现。为了揭示这种过敏性疾病特征模式背后的基因，我们对12个群体中的婴儿湿疹和儿童哮喘进行了多阶段全基因组关联研究，包括2428例病例和17034例对照。在此，我们报告了两个新的位点，它们特异性地针对湿疹加哮喘的联合表型，首次与过敏性疾病相关；rs9357733位于6号染色体p12.3上的EFHC1中（比值比1.27；P = 2.1×10^(-8)），rs993226位于12号染色体q21.3上的TMTC2和SLC6A15之间（比值比1.58；P = 5.3×10^(-9)）。在全基因组水平上确定的其他易感位点包括FLG（1q21.3）、IL4/KIF3A（5q31.1）、AP5B1/OVOL1（11q13.1）、C11orf30/LRRC32（11q13.5）和IKZF3（17q21）。我们表明，主要与湿疹相关的位点增加了特应性进程的风险。我们的研究结果表明，湿疹可能在湿疹后哮喘的发展中起重要作用。
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