Scientists uncovered Asthma’s genetic origins

Researchers are combing through mountains of data to understand a disease that afflicts growing numbers of children and adults.


According to a recent Global Burden of Disease Study, more than 334 million people worldwide may suffer from this common chronic disease. In the United States, the Centers for Disease Control and Prevention reports that asthma afflicts an estimated 25 million people, about 8 percent of the population.

It hits children even harder; about 10 percent of them have this respiratory malady that hinders breathing. Asthma accounts for a quarter of all emergency room visits and more than 500,000 hospitalizations in the United States each year.

According to an estimate, asthma kills about 3,500 Americans annually and the peculiar thing is that most of these deaths are preventable with proper treatment. It also contributes to another 7,000 deaths.

Notwithstanding the foregoing, the financial tab is steep. The United States spends an estimated $56 billion every year for medical care. All these rising numbers are alarming so among certain populations.

Asthma is increasingly damaging to economies and public health which has been recognized by researchers and policymakers. In recent years, the United Nations has spotlighted the disease several times, citing it as a growing threat to global health and economic development.

The Global Asthma Network, formed to improve asthma care internationally, has published two reports about the disease, most recently in 2014. In 2013 the World Health Organization (WHO) called for a global action plan and international monitoring of asthma and other non-communicable diseases.

Genetic Sleuthing

At the very first instance, it is essential to recognize the causes to fight asthma effectively. Scientists have established that the disease stems from some combination of genetic inheritance and environmental factors such as air pollution, chemical substances and indoor and outdoor allergens like smoke and pollen. But many of these things are still unknown.

According to the WHO’s most recent fact sheet, “The fundamental cause of asthma are not completely understood.” Science is still many years away from solving the mystery of the biological causes of this disease.

Andrew T. De Wan, an associate professor in the Department of Chronic Disease Epidemiology, said, “Asthma is what we in the field of genetic epidemiology classify as a complex trait.”

“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.”

Previously, researchers have postulated associations between asthma and more than 400 genes, a huge pool of possibilities. But that’s just the start of this disease’s complexity. For detecting asthma’s foundations, researchers must identify the specific mutations within them that point to the disease along with causative genes.

Further, the genes that may affect risk for asthma seem to connect or interact in myriad combinations, and these are not necessarily consistent. The combinations that lead to asthma seem to vary from person to person and group to group.

All of these possible genetic combinations may further be influenced or not, by their response in accordance with the environment they individually or collectively face. A cluster of genetic characteristics that leads to asthma in one person might or not affect others, possibly either because of other genetic factors or of differences in the individuals’ environments.

To worsen things further, a study published recently in JAMA (The Journal of the American Medical Association), found that a third of 600 adults diagnosed with asthma didn’t actually have the disease, which casts some doubt on statistics about asthma.

De Wan works to cut through this welter, winnowing out the genes or gene combinations that probably don’t lead to asthma and verifying those that look promising.

He said, “A lot of my research is focused on dealing with this mixed bag of results to get a better biological understanding of asthma.” 

Much of this is done through large-scale statistical analysis of genetic data, looking at big populations for mutations linked to the disease. A recent study that De Wan co-authored, for instance, surveyed the scientific literature to find genes that have been associated with asthma.

De Wan and his colleagues identified 251 of them and then tried to replicate those findings through a genetic analysis of an independent population. (They recently updated their search and mention the current count of genes reportedly associated with asthma is now over 400.)

In their statistical analysis, De Wan and his colleagues got minor hits on several genes and also identified one previously unassociated gene (RAD50), but they were unable to replicate any links to asthma in the vast majority of reported genes.

De Wan noted, “That doesn’t necessarily mean these genes aren’t implicated in the disease, but the caveat in our paper is that there may be many false positives in our initial literature search. That’s one reason genetic epidemiologists require that results be replicated.”

Though many findings of genetic contributions to asthma may seem inconsistent and ambiguous, the picture is slowly coming into better focus as more studies connect the same genes, such as ADAM33 and ORMDL3, to the disease.

De Wan added, “I think the true number of genes that contribute in some way to the risk of developing asthma is well over 100.”

Further, he stated, “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. We’re trying to understand which inherited genetic variants are contributing to an individual’s risk of develop- ing 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 analysis entails sequencing the genomes of thousands of people and then looking for mutations, and combinations of mutations, common to people with asthma. If De Wan and others can identify the ones that contribute to asthma, they may be able to predict who will develop the disease. Once that’s possible, so is prevention.

De Wan said, “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.”

In near future genetic markers could help identify which individuals will respond and which will not to certain drugs and treatments, to open the way to effective targeted therapies.

Genetic knowledge might also make it possible to predict which environmental factors should be avoided by people with a certain combination of mutations.

De Wan said, “The goal is to reduce the overall severity of asthma and it’s public health costs.”

Andrew De Wan and Yasmmyn Salinas extract genomic DNA from saliva samples collected as part of FAstGen, a study of genetic variants contributing to asthma susceptibility in families that have multiple children with asthma. The DNA samples are currently being sequenced to reveal all of the genetic variants in the protein-coding regions of the genome.

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