Allergic diseases – eczema, wheeze and rhinitis, often present as heterogeneous phenotypes in children. Examining genetic associations of specific symptomatic patternsmay render an enhanced understanding of the underlying biological mechanisms.

A new study published in Clinical and Experimental Allergy examined associations between allergic disease-related variants identified in a recent genome-wide association study and latent classes of allergic diseases (LCADs) in two population-based birth cohorts.

This study used eight previously defined LCADs among subjects of 1-11 years of age –no disease;atopic march;persistent eczema and wheeze;persistent eczema with later-onset rhinitis;persistent wheeze with later-onset rhinitis;transient wheeze;eczema only; and rhinitis only.

The results revealed a strong evidence for differential genetic associations across LCADs. Associations between the polygenic risk score (PRS) and LCADs in Manchester Asthma and Allergy Study (MAAS) were markedlysimilartoThe Avon Longitudinal Study of Parents and Children (ALSPAC). On the other hand, twosingle nucleotide polymorphisms (SNPs) – a protein truncating variant in filaggrin and a SNP within an intron of GSDMB gene, had evidence for differential association. The filaggrin locus was differentially associated across LCADs that included eczema, with stronger associations for LCADs with comorbid wheeze and rhinitis. Whereas, the GSDMB locus was equally associated across LCADs that included wheeze.

The findings disclosed complex but distinct patterns of genetic associations with LCADs, suggesting that heterogeneous mechanisms underlie individual disease trajectories. It was speculated that establishing the combination of allergic diseases with which each genetic variant is associated may inform therapeutic development and/or predictive modelling.