GWAS Study Finds Differences Between Onset of Adult, Pediatric Asthma

A genome-wide association study (GWAS) found that childhood-onset asthma was associated with nearly 3 times as many genes as asthma that develops in adults, in which environmental factors play a much bigger role.

Genes associated with adult-onset asthma were a subset of those associated with asthma in children younger than 12. While immune-mediated mechanisms drive disease progression in both children and adults, the effects are smaller in adults.

Reported in Lancet Respiratory Medicine, the study is the largest thus far to examine the differences in genetic risk factors for childhood-onset and adult-onset asthma. It is already known that childhood-onset asthma and adult-onset asthma differ with respect to sex ratios, exacerbation triggers, associated comorbidities, severity, and possible genetic risk factors.

The researchers, from the University of Chicago, defined childhood-onset asthma as occurring in those younger than 12 years of age. Adult-onset cases were defined as ones where the disease developed between the ages of 26 and 65.

The study used data from the UK Biobank, a large long-term study that concentrates on the contributions of genetic predisposition and environmental exposure to the development of disease.

The researchers used data from 37,846 British individuals who reported an asthma diagnosis, including 9433 adults who developed asthma as children, 21,564 adults with adult-onset asthma, and an additional 6849 young adults who developed asthma between the ages from 12 to 25.

They also developed a control group of 318,237 people 38 years old or older who did not have asthma.

The GWAS of childhood and adult asthma revealed 61 independent asthma-related genes. Fifty-six of the 61 were significant in childhood-onset asthma and 19 were significant in adult-onset disease. Twenty-eight of those loci, or regions of the human genome, had not been previously catalogued; 17 were significant for children only. Only 1 was significant only for adult-onset asthma.

Childhood-onset genes were highly expressed in epithelial cells, which are similar to what is seen with childhood eczema, food allergy, and allergic rhinitis.

The researchers said that the finding supports the idea that pediatric asthma “is due to impaired barrier function in the skin and other epithelial surfaces,” which allows for sensitization to food and other allergens, as well as respiratory and wheezing illnesses in early life.

They suggested that precision medicine should be further refined to account for age of asthma onset, saying that it is possible that the most asthma effective treatments will differ between these 2 groups.

The National Institutes of Health funded the study.

Reference

Pividori M, Schoettler N, Nicolae DL, Ober C, Kyung Im HK. Shared and distinct genetic risk factors for childhood-onset and adult-onset asthma: genome-wide and transcriptome-wide studies [published online April 30, 2019]. Lancet Respir Med. doi: 10.1016/S2213-2600(19)30055-4.