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

TitelMeta-analysis identifies seven susceptibility loci involved in the atopic march.
MedientypJournal Article
Jahr der Veröffentlichung2015
AutorenMarenholz I, Esparza-Gordillo J, Rüschendorf F, Bauerfeind A, Strachan DP, Spycher BD, Baurecht H, Margaritte-Jeannin P, Sääf A, Kerkhof M, Ege M, Baltic S, Matheson MC, Li J, Michel S, Ang WQ, McArdle W, Arnold A, Homuth G, Demenais F, Bouzigon E, Söderhäll C, Pershagen G, de Jongste JC, Postma DS, Braun-Fahrländer C, Horak E, Ogorodova LM, Puzyrev VP, Bragina EYu, Hudson TJ, Morin C, Duffy DL, Marks GB, Robertson CF, Montgomery GW, Musk B, Thompson PJ, Martin NG, James A, Sleiman P, Toskala E, Rodriguez E, Fölster-Holst R, Franke A, Lieb W, Gieger C, Heinzmann A, Rietschel E, Keil T, Cichon S, Nöthen MM, Pennell CE, Sly PD, Schmidt CO, Matanovic A, Schneider V, Heinig M, Hübner N, Holt PG, Lau S, Kabesch M, Weidinger S, Hakonarson H, Ferreira MAR, Laprise C, Freidin MB, Genuneit J, Koppelman GH, Melén E, Dizier M-H, A Henderson J, Lee YAe
JournalNat Commun
Volume6
Pagination8804
Datum der Veröffentlichung2015 Nov 06
ISSN2041-1723
SchlüsselwörterAdaptor Proteins, Vesicular Transport, Adolescent, Adult, Amino Acid Transport Systems, Neutral, Asthma, Calcium-Binding Proteins, Carrier Proteins, Child, Child, Preschool, Dermatitis, Atopic, Disease Progression, DNA-Binding Proteins, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Ikaros Transcription Factor, Interleukin-4, Kinesin, Logistic Models, Male, Membrane Proteins, Middle Aged, Neoplasm Proteins, Nerve Tissue Proteins, Nuclear Proteins, Phenotype, Polymorphism, Single Nucleotide, Receptor, Fibroblast Growth Factor, Type 1, Repressor Proteins, Transcription Factors, Young Adult
Zusammenfassung

<p>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. </p>

DOI10.1038/ncomms9804
Alternate JournalNat Commun
PubMed ID26542096
PubMed Central IDPMC4667629
Grant List102215 / / Wellcome Trust / United Kingdom
G0601361 / / Medical Research Council / United Kingdom
MC_PC_15018 / / Medical Research Council / United Kingdom