Genetic Risk Factors for Childhood-Onset vs Adult-Onset Asthma

The genetic risk factors for adult-onset asthma are mostly a subset of the genetic risk factors for childhood-onset asthma, according to results published in The Lancet Respiratory Medicine.

The study included participants with asthma, including adults with childhood-onset asthma (onset before age 12 years), adults with adult-onset asthma (onset between 26 and 65 years of age), and adults without asthma (controls). The researchers performed genome-wide association studies for childhood-onset asthma and adult-onset asthma compared with shared controls and for age of asthma onset in all asthma cases. The genome-wide significance threshold was P <5×10^-8.

Of 376,358 white British individuals from the United Kingdom Biobank, the researchers identified 9433 adults with childhood-onset asthma, 21,564 adults with adult-onset asthma, and 6849 young adults with asthma onset between the ages of 12 and 25 years.

The researchers detected 61 independent asthma loci. Of these, 23 were childhood-onset specific, 1 was adult-onset specific, and 37 were shared. They determined that 19 loci were associated with age of asthma onset.

The results indicated that the most significant asthma-associated locus was at 17q12 (odds ratio 1.406; 95% CI, 1.365-1.448; P =1.45 × 10^–111) in the childhood-onset genome-wide association studies.

For childhood-onset specific loci, genes were most highly expressed in the skin, blood, and small intestine. For adult-onset specific loci, the genes were most highly expressed in the lung, blood, small intestine, and spleen.

The researchers found that the onset of disease in childhood was associated with additional genes that had relatively large effect sizes, with the largest odds ratio observed at the filaggrin gene locus at 1q21.3 (1.970; 95% CI, 1.823-2.129).

“Combined with gene expression and tissue enrichment patterns, we suggest that the establishment of disease in children is driven more by dysregulated allergy and epithelial barrier function genes, whereas the cause of adult-onset asthma is more lung-centred and environmentally determined, but with immune-mediated mechanisms driving disease progression in both children and adults,” the researchers wrote.

Reference

Pividori M, Schoettler N, Nicolae DL, Ober C, Im HK. Shared and distinct genetic risk factors for childhood-onset and adult-onset asthma: genome-wide and transcriptome-wide studies [published online April 26, 2019]. Lancet Respir Med. doi:10.1016/ S2213-2600(19)30055-4