Scientists have identified a gene that is strongly associated with a risk of developing childhood onset asthma, a discovery that may lead to better treatments for the common chronic ailment.

In a study of more than 2,000 children, scientists from the University of Michigan and colleagues from London, France and Germany found genetic markers on chromosome 17 that dramatically increase a child's risk for asthma.

Children with this marker had higher levels of a new gene called ORMDL3 in their blood, which occurs in higher amounts in children with asthma. The presence of the disease-associated version of ORMDL3 increases the risk of asthma by 60-70 per cent, the study suggests.

"These novel findings do not explain completely how asthma is caused, but they do provide a further part of the gene-environment jigsaw that makes up the disease," says Dr. Miriam Moffatt of the National Heath and Lung Institute, Imperial College, London, one of the first authors of the study.

The study appears in the journal Nature.

William Cookson, a researcher at London's Imperial College's National Heart and Lung Institute, who coordinated the study, says the discovery could one day lead to new treatments.

"I think eventually it will lead to new therapies because it points to a specific biological molecular pathway. Once we understand the biology and we know the players, it's possible to target with specific drugs."

Moffatt says the next step is to find other genes that have a smaller effect on asthma development and relate those genes to environmental factors that increase asthma risk.

ABSTRACT

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

Miriam F. Moffatt, Michael Kabesch, Liming Liang, Anna L. Dixon, David Strachan, Simon Heath, Martin Depner, Andrea von Berg, Albrecht Bufe, Ernst Rietschel, Andrea Heinzmann, Burkard Simma, Thomas Frischer, Saffron A. G. Willis-Owen, Kenny C. C. Wong, Thomas Illig, Christian Vogelberg, Stephan K. Weiland, Erika von Mutius, Gonçalo R. Abecasis, Martin Farrall, Ivo G. Gut, G. Mark Lathrop & William O. C. Cookson

Asthma is caused by a combination of poorly understood genetic and environmental factors. 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 reticulum.

The results indicate that genetic variants regulating ORMDL3 expression are determinants of susceptibility to childhood asthma.

• Abstract in Nature