Pinpointing the genes most responsible for asthma has proven to be a daunting task with too many genetic possibilities to sift through.

Modern researchers have postulated associations between asthma and more than 400 genes, but to discover the ailment’s foundations they must identify both the causative genes and the specific mutations within them that point to the disease.

The genes that may impact the risk for asthma seem to connect or interact in a number of combination that are not necessarily consistent, where the combination that leads to asthma differs in each individual.

However, researchers from Yale University have begun to connect the same genes—including ADAM33 and ORMDL3—to asthma, a major step forward in identifying the origin of the disease.

“I think the true number of genes that contribute in some way to the risk of developing asthma is well over 100,” Andrew DeWan, M.P.H., Ph.D., an associate professor in the Department of Chronic Disease Epidemiology, said in a statement.

The researchers used a combination of high-speed sequencing with the growing quantity and availability of genetic data.

“To detect the small effects of these genetic variants on asthma, we need much larger sample sizes and we’re now getting to that point,” DeWan said. “We’re trying to understand which inherited genetic variants are contributing to an individual’s risk of developing asthma by looking in large populations, and these big data sets will give us the statistical power to find what is really a needle in a haystack.”  

The researchers originally identified 251 genes that they then attempted to replicate through a genetic analysis of an independent population. The analysis resulted in minor hits on several genes and one previously unassociated gene, but they were unable to replicate any links to asthma in the vast majority of the genes.

DeWan explained that the results do not necessarily mean that the genes are not implicated in asthma, but there may be several false positives in the initial literature search.

“That’s one reason genetic epidemiologists require that results be replicated,” he said. 

Scientists know that asthma is caused by a combination of genetic inheritance and environmental factors including air pollution, chemical substances and indoor and outdoor allergens. However, the fundamental cause of asthma remains relatively unknown.

“Asthma is what we in the field of genetic epidemiology classify as a complex trait,” DeWan said. “Genetic characteristics inherited from your parents make about a 50 percent contribution to the risk of developing asthma, but there is also a large component that is not inherited—all sorts of environmental influences.”

By identifying the genes that contribute to asthma, researchers may be able to predict who will develop the disease.

“If we can understand the biological processes that cause asthma we can develop better treatments for it and intervene at a pharmaceutical level to prevent or lessen the symptoms,” DeWan said.

The research team is also examining a link between asthma and obesity.

“One of the hypotheses is that they are controlled by the same metabolic pathways, so there is probably a set of genes that affects both diseases,” Yasmmyn Salinas, a Ph.D. candidate in DeWan’s lab, said in a statement. “I will look for these genes by studying the whole genome of a large adult population.”

Genetic markers could also help identify which individuals will respond, or not respond, to certain drugs and treatments, opening the way to effective targeted therapies.   

According to a recent Global Burden of Disease Study, there are 334 million people worldwide suffering from Asthma with the Centers for Disease Control and Prevention estimating about 25 million sufferers in the U.S.

Medical care, absences from work and school, as well as premature deaths account for a loss of about $56 billion in the U.S. annually.