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A New Genetic Link to Childhood Asthma

Asthma with severe exacerbation is the most common reason for the hospitalisation of young children. These exacerbations are generally triggered by recurrent and aggressive respiratory infections. However, the causative factors underlying these infections are poorly understood. A recent study, published in Nature, used a Genome-wide Association Study (GWAS) to further understand the genetic basis of childhood asthma.

Childhood Asthma

The heritability of Asthma is ~50%. Although previous GWAS studies have identified several common susceptibility variants, asthma is a highly heterogenous disorder and the known genes can only explain a small proportion of disease variance. This study covered 68,281 individuals and conducted a GWAS specifically focused on genetic variants.

Genetic Susceptibility

Through examining severe asthma cases, the study identified a new susceptibility locus for early childhood asthma. This genetic locus is located on chromosome 19 near the FUT2 gene. The FUT2 gene encodes an enzyme called fucosyltransferase 2 which is necessary for the secretion of ABO blood group antigens in body fluids and epithelial surfaces. Individuals with an active copy of this gene are referred to as ‘secretors’. These secretors were found to be more likely to develop early childhood asthma.

Their results also suggest that the presence of A or B antigens further increase the risk. In comparison, O antigens had no significant effect on susceptibility. This is interesting as AB antigens are glycans. The presentation of specific glycans in mucus and on epithelial surfaces is known to play a role in susceptibility to viral and bacterial infections. In turn, these infections are the main trigger of asthmatic symptoms, particularly in childhood. Therefore, the study presents a biologically plausible mechanism for the increased susceptibility of developing childhood asthma.

Respiratory Infections

This FUT2-ABO genotype was also associated with specific respiratory infections resulting from the bacterium Streptococcus pneumoniae. This bacterium is known to cause a range of airway infections, including pneumonia, and is a common trigger for childhood asthma. Studies have shown that microbes often target host glycans for nutrition and cell invasion purposes. Furthermore, fucosylations are known to play a key role for S. pneumoniae virulence. The FUT2 and ABO genetic variants also share several biological pathways, and are known to interact. These factors further support the study hypothesis.

Epistasis in Childhood Asthma

There are high rates of phenotypic variance between those who suffer from asthma, much of which has not been genetically defined. It is likely that much of this variance results from interacting regions of the genome, known as epistasis. This study demonstrates the importance phenotype-specificity to detect gene-gene interactions as strong interactions between FUT2 and ABO genes was only seen in those with severe asthma cases and may not otherwise have been uncovered.


The results suggest that children with genetically determined ‘secretor’ status and A/B genotypes have an increased risk of S. pneumoniae infections. If future studies confirm these findings, it could aid the development of personalised treatments or infection prevention. However, the results must first be replicated across different populations and a clear cause behind these findings must be established.

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