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Moffatt, M.F.* ; Kabesch, M.* ; Liang, L.* ; Dixon, A.L.* ; Strachan, D.* ; Heath, S.* ; Depner, M.* ; von Berg, A.* ; Bufe, A.* ; Rietschel, E.* ; Heinzmann, A.* ; Simma, B.* ; Frischer, T.* ; Willis-Owen, S.A.* ; Wong, K.C.* ; Illig, T. ; Vogelberg, C.* ; Weiland, S.K.* ; von Mutius, E.* ; Abecasis, G.R.* ; Farrall, M.* ; Gut, I.G.* ; Lathrop, G.M.* ; Cookson, W.O.*

Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma.

Nature 448, 470-474 (2007)
DOI
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Asthma is caused by a combination of poorly understood genetic and environmental factors1, 2. We have systematically mapped the effects of single nucleotide polymorphisms (SNPs) on the presence of childhood onset asthma by genome-wide association. We characterized more than 317,000 SNPs in DNA from 994 patients with childhood onset asthma and 1,243 non-asthmatics, using family and case-referent panels. Here we show multiple markers on chromosome 17q21 to be strongly and reproducibly associated with childhood onset asthma in family and case-referent panels with a combined P value of P < 10-12. In independent replication studies the 17q21 locus showed strong association with diagnosis of childhood asthma in 2,320 subjects from a cohort of German children (P = 0.0003) and in 3,301 subjects from the British 1958 Birth Cohort (P = 0.0005). We systematically evaluated the relationships between markers of the 17q21 locus and transcript levels of genes in Epstein–Barr virus (EBV)-transformed lymphoblastoid cell lines from children in the asthma family panel used in our association study. The SNPs associated with childhood asthma were consistently and strongly associated (P < 10-22) in cis with transcript levels of ORMDL3, a member of a gene family that encodes transmembrane proteins anchored in the endoplasmic reticulum3. The results indicate that genetic variants regulating ORMDL3 expression are determinants of susceptibility to childhood asthma.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
ISSN (print) / ISBN 0028-0836
e-ISSN 1476-4687
Zeitschrift Nature
Quellenangaben Band: 448, Heft: 7152, Seiten: 470-474 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)