Research Profile – The Asthma Lottery

A UBC researcher examines how genetics and environmental factors determine who develops asthma.

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Asthma is a common yet complex disease that has both genetic and environmental causes. It currently affects about 300 million people globally, and rates are increasing worldwide. It can occur at any age and change its features throughout the course of a person's life.

Dr. Denise Daley is trying to uncover the causes of asthma. She is an assistant professor of medicine at the University of British Columbia, and Canada Research Chair in Genetic Epidemiology of Complex Diseases.

She and her research team are working not only to identify specific genes involved in asthma, but also to determine how exposures to things such as allergens, pollutants or viruses in the environment interact with those genes to trigger asthma.

"What we want to do is understand why asthma is on the increase, and what contribution gender, genes and the environment make in the development of asthma," she said. While a number of genes have been identified as being linked to asthma, "not everyone has the same constellation of genes that predispose them to the disease."

Dr. Daley has been involved in genome-wide association studies. In these studies, researchers focus on common genetic variants found in different people that are associated with a trait – such as a specific disease. Typically, these studies compare the DNA of two groups of people (people with a disease, and those without) to determine gene segments that are 'suspect' and may be associated with the disease. It helps identify asthma susceptibility genes.

But even if a person carries genes that put them at risk for the disease, they don't necessarily develop asthma, simply because the disease is not caused by genes alone. "With something such as asthma, the contribution of the environment through gene-environment interactions must be taken in account too," Dr. Daley said.

In fact, a recent study by Dr. Daley's team found that interventions to reduce the prevalence of asthma and allergy worked to prevent the development of an allergy in some children but not others – depending on which variation of an allergy-related gene called CD14 that individual children had. Eventually, it may be possible to use genetic tests to determine what treatment or prevention strategies will work on which people.

But how does one determine which genes and which environmental exposures result in an increased risk for asthma? Some research suggests that exposure to allergens or cigarette smoke can change the expression of certain genes in a fetus, and that this change may alter lung development. As a result, once a baby is born, it has a higher risk of suffering from asthma.

According to Dr. Daley, the best way to study environmental factors that make people susceptible to childhood asthma is to follow birth cohorts over long periods of time – starting from pregnancy. This is exactly what she and her team are doing. They are drawing on data from two Canadian birth cohorts: the Canadian Asthma Primary Prevention Study (CAPPS), and the Manitoba-based Study of Asthma Genes and Environment (SAGE).

Launched in 1995, CAPPS assessed a multi-faceted intervention strategy in children with a family history of asthma or allergic disease. The intervention worked, although more research is needed to determine which facet of the intervention helped guard against asthma.

In the SAGE project, Dr. Daley and her team sent surveys to the families of 16,320 children born in 1995. Seven hundred and twenty three of the children and their parents were recruited for genetic studies. The researchers assessed the children for asthma and allergies and collected environmental samples. Information from SAGE will help determine why asthma rates are higher in urban versus rural settings.

"You can't change your genes but if you can modify the environment, you might be able to prevent asthma," Dr. Daley said.

The origins of asthma appear to lie in the prenatal and early postnatal period. Long-term investigations, genetic studies and looking at multiple environmental factors will shed light on just how asthma develops in some people, and why it doesn't in others.

"It is only after understanding these effects that one can hope to design intervention and prevention studies for asthma that can be effective on a population level," she said.

"You can't change your genes but if you can modify the environment, you might be able to prevent asthma."
– Dr. Denise Daley, University of British Columbia