Epigenetics Study Could Help Predict Asthma Risk

Denise Daley, PhD

A better look at an individual’s epigenetic clock could help better understand the risk of developing asthma.

A team, led by Denise Daley, PhD, University of British Columbia, used the Horvath age prediction algorithm to examine the predicted biological age of participants with and without asthma in a pair of cohorts based in Canada.

Methylation is considered a crucial DNA epigenetic modification that can be impacted by environmental exposures, age, and disease.

Recently, investigators discovered that the epigenetic clock, which evaluates age compared to predicted biological age, could be an emerging tool in evaluating the effect of a disease like asthma or environmental exposure on the epigenetic profile of an individual.

The Horvath epigenetic clock is a frequently used algorithm able to predict the biological age based on the methylation levels at 353 CpG sites.

In an abstract originally planned for presentation at the American Thoracic Society (ATS) 2020 International Conference, investigators collected 812 samples from the Canadian Asthma Primary Prevention Study (CAPPS, n = 632 samples) and the Saguenay-Lac Saint-Jean (SLSJ, n = 180 samples) cohorts.

The CAPPS study is a prospective, longitudinal birth cohort, following 549 children at a high-risk of developing asthma from birth to age 15. The investigators identified longitudinal asthma and allergy phenotypes assessed at 12 and 24 months, as well as 7 and 15 years. The study also included detailed exposure assessments.

In the SLSJ trial, the investigators examined multigenerational families of French Canadian descent, from which a 3 generational triads were selected to evaluate generational effects of methylation.

The investigators performed methylation sequencing on the 812 samples using Illumina’s TruSeq Methyl Capture library. They then used the Horvath epigenetic algorithm to predict the age using methylation profiles and compared it to relative biological age.

“Preliminary results show that asthmatic children are older on the epigenetic clock compared to children without asthma (P = 0.02),” the authors wrote. “Upon further examination of the CAPPS cohort, in the Year 7 samples (P = 0.01), the asthma cases had a higher epigenetic age than the asthma controls. This trend was reversed at Year 15 (P = 0.74) and asthmatic adults from the SLSJ cohort are younger on the epigenetic clock, which tracks with the gender reversal seen in asthma.”

In 2018, 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.

They found a total of 878 genetic variants in 18 loci associated with asthma risk. The study showed asthma-related genetic variants tend to be located near epigenetic markers in immune cells.

The 2018 study, coupled with the current work by Daley and colleagues, suggests epigenetics can help shed light on asthma patients.

“These findings suggest that epigenetic studies may provide insights into the mechanisms associated with asthma,” the authors wrote.

The study, “Asthma, Gender and the Epigenetic Clock,” was published online by the ATS International Conference.