Major Meta-analysis Yields New Asthma Risk Insights

Dan L. Nicolae, PhD

A massive new meta-analysis offers the most comprehensive window to date into the genetic associations of asthma.

An international team of researchers conducted a meta-analysis of asthma genome-wide association studies from around the world, encompassing 23,948 cases of asthma and more than 100,000 controls. The authors discovered new asthma risk factors, and also confirmed existing knowledge about the genetics of the condition.

“We identified 5 new asthma loci, found 2 new associations at 2 known asthma loci, established asthma associations at 2 loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed 9 known loci,” the authors wrote.

The study was worked on by 45 research groups from around the world and included patients spanning a broad range of ancestries, including European, African, Latino, and Japanese. They found a total of 878 genetic variants in 18 loci associated with asthma risk.

Dan L. Nicolae, PhD, a professor in the department of human genetics at the University of Chicago, told MD Magazine there are a number of reasons such a large meta-analysis was necessary.

“Previous studies showed that the genetic risk factors have low effects and hence require very large sample sizes for discovery,” Nicolae said. “Also the heterogeneity in disease prevalence suggested that a multi-ancestry study gives us a better chance for discovery of novel and relevant common genetic risk factors.”

Nicolae also said the study was designed with the goal of getting a comprehensive catalog of asthma genetic loci. That information will help better zero in on how environmental factors affect asthma risk.

The study showed asthma-related genetic variants tend to be located near epigenetic markers in immune cells.

The research opens up the potential for significant follow-on research, he said.

“We also discovered a strong genetic overlap with other multifactorial diseases, including autoimmune diseases, another area for further research,” Nicolae noted.

The study adds considerably to the body of knowledge around asthma, but Nicolae said because environmental factors play such a major role in asthma risk, it’s not yet feasible to predict which patients might or might not get asthma.

“Prediction is difficult, but prevention is an open area of investigation where knowledge from these genetic studies is used to understand the molecular pathways most relevant for asthma etiology,” he said.

Researchers are currently working to look at how environmental factors affect asthma risk at different stages in life, such as prenatal and early childhood, Nicolae added.

Asthma is thought to affect between 10% and 20% of children worldwide, though rates vary widely based on environmental and socioeconomic factors.

Moving forward, Nicolae said a remaining gap in the research is a long-term study focused on genetics.

“To me, the most exciting avenue is to better understand the mechanisms behind these asthma associations using a combination of genomics tools on longitudinal studies or birth cohorts (children enrolled at birth and studied longitudinally until the age they could be diagnosed for asthma),” he said.

The study, “Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks,” was published in Nature Genetics last month.

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