Asthma: Genetic Risks of Development and Course

Daniel Belsky, PhD NIA Postdoctoral Fellow Center for the Study of Aging and Human Development Duke Interview with:

Daniel Belsky, PhD
NIA Postdoctoral Fellow
Center for the Study of Aging and Human Development
Duke University

Polygenic risk and the development and course of asthma: an analysis of data from a four-decade longitudinal study What are the main findings of the study?

Dr. Belsky : We looked to the largest-ever genome-wide association study of asthma (that study by the GABRIEL Consortium included more than 26,000 individuals) to identify genetic variants that could be used to construct a genetic profile of asthma risk. We then turned to The Dunedin Multidisciplinary Health and Development Study, a unique cohort of 1,000 individuals who have been followed from birth through their fourth decade of life with extensive measurements of asthma and related traits. We computed a “genetic risk score” for each person based on the variants identified in GWAS.  Then, we looked at who developed asthma, when they developed asthma, and what that asthma looked like in terms of allergic response and impaired lung function.

What we found:

(1) People with higher genetic risk scores were more likely to develop asthma and they developed asthma earlier in life.

(2) Among children who developed asthma, the ones at higher genetic risk were more likely to have persistent asthma through midlife.

(3) Genetic risk was specifically associated with allergic asthma that resulted in chronic symptoms of impaired lung function.

(4) People with higher genetic risk score developed more severe cases of asthma. As compared to people with a lower genetic risk, they were more often absent from school and work because of asthma and they were more likely to be hospitalized for asthma.

(5) The genetic risk score provided new information about asthma risk that could not be obtained from a family history. Were any of the findings unexpected?

Dr. Belsky : We were a little surprised to find that people with higher genetic risk scores did not necessarily have strong family histories of asthma, and vice versa–people who had many relatives with asthma often had very low genetic risk scores. We have seen this same pattern of results now in other studies we’ve done on smoking and obesity, and other investigators have found similar results for type-2 diabetes and some cancers. So this lack of overlap between genotypic and family history risk looks like a real thing. One possible explanation for this observation is that family histories capture information about environmental risks and about interactions between genetic and environmental risk factors. What should clinicians and patients take away from your report?

Dr. Belsky : Genetic tests to determine whether children will develop asthma or whether their asthma will remit or persist are not yet possible.  Our work suggests that genetic information may, in the future, be able to improve clinical risk assessments. In the mean time, the genetic risk score we studied will be a useful tool for research. What recommendations do you have for future research as a result of this study?

Dr. Belsky : Future research should focus on the question of how genetic risks interact with environmental exposures including pollution and other factors that affect air quality. Research is also needed to test how well our findings generalize to non-European populations and to investigate how the genetic risks we studied affect asthma in later life.


Polygenic risk and the development and course of asthma: an analysis of data from a four-decade longitudinal study
Dr Daniel W Belsky PhD,Prof Malcolm R Sears MB,Robert J Hancox MD,HonaLee Harrington BS,Renate Houts PhD,Prof Terrie E Moffitt PhD,Karen Sugden PhD,Benjamin Williams BSc,Prof Richie Poulton PhD,Prof Avshalom Caspi PhD
The Lancet Respiratory Medicine – 28 June 2013
DOI: 10.1016/S2213-2600(13)70101-2

Please also visit Dr. Belsky’s Website for more information on this topic

Last Updated on October 21, 2015 by Marie Benz MD FAAD