A Large-Scale, Consortium-Based Genomewide Association Study of Asthma
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ABSTRACT:
PROVIDER: EGAS00000000077 | EGA |
REPOSITORIES: EGA
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A large-scale, consortium-based genomewide association study of asthma.
Moffatt Miriam F MF Gut Ivo G IG Demenais Florence F Strachan David P DP Bouzigon Emmanuelle E Heath Simon S von Mutius Erika E Farrall Martin M Lathrop Mark M Cookson William O C M WOCM
The New England journal of medicine 20100901 13
<h4>Background</h4>Susceptibility to asthma is influenced by genes and environment; implicated genes may indicate pathways for therapeutic intervention. Genetic risk factors may be useful in identifying subtypes of asthma and determining whether intermediate phenotypes, such as elevation of the total serum IgE level, are causally linked to disease.<h4>Methods</h4>We carried out a genomewide association study by genotyping 10,365 persons with physician-diagnosed asthma and 16,110 unaffected perso ...[more]
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Project description:Asthma is caused by a combination of poorly understood genetic and environmental factors. We found 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 < 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 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 encode transmembrane proteins anchored in the endoplasmic reticulum. The results indicate that genetic variants regulating ORMDL3 expression are determinants of susceptibility to childhood asthma. Keywords: association study, global gene expression, asthma, ORMDL3
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