Sorting through hundreds of genetic risk variants for asthma, Australian scientists – with input and data from researchers at 23andMe – have identified an association between asthma and the expression of four genes, a finding that could aid efforts for treating the chronic disease that impacts an estimated 300 million people worldwide.
Published in The Journal of Allergy and Clinical Immunology, the new study – led by asthma researchers at the QIMR Berghofer Medical Research Institute in Brisbane, Australia – took an innovative approach to identifying these four genes, developing a gene-based test and software the researchers dubbed EUGENE. This approach combines information from genome wide association studies for asthma with expression Quantitative Trait Loci, or eQTLs, known locations in the genome that influence how that gene involved in asthma are expressed.
Because there are so many different genetic risk variants for asthma – potentially thousands of variants – the researchers were looking for a way to improve the power of traditional genome wide association studies for identifying genes that have a functional role in the disease.
This approach helped researchers to find four genes B4GALT3, USMG5, P2RY13 and P2RY14. Two of those genes – P2RY13 and P2RY14 – are both associated with impaired lung function in asthmatics. P2RY14 also is associated with elevated white blood cell counts, which is often seen during a heightened inflammatory response.
Beyond identifying these four novel asthma risk genes, the lead researcher Manuel Ferreira and his team took these findings a step further. They did functional studies in mice to look at changes in the expression of two of the genes – P2RY13 and P2RY14. The researchers found that increased expression of these two genes in mice resulted in impaired lung function and an increase in eosinophil counts – the white blood cells that are often used as biomarkers for asthma. These findings may aid in research into treatments for asthma, according to the study authors.
The study appears in the Journal of Allergy and Clinical Immunology.