Transcriptomics of atopy and atopic asthma in white blood cells from children and adolescents

Early allergic sensitisation (atopy) is the first step in the development of allergic diseases such as atopic asthma later in life. Genes and pathways associated with atopy and atopic asthma in children and adolescents have not been well characterised. A transcriptome-wide association study of atopy and atopic asthma in white blood cells or whole blood was conducted in a cohort of 460 Puerto Ricans aged 9–20 years (EVA-PR) and in a cohort of 250 Swedish adolescents (BAMSE). Pathway enrichment and network analyses were conducted to further assess top findings, and classification models of atopy and atopic asthma were built using expression levels for the top differentially expressed genes. In a meta-analysis of the study cohorts, both previously implicated genes ( e.g. , IL5RA and IL1RL1 ) and genes not previously reported in TWAS (novel) were significantly associated with atopy and/or atopic asthma. Top novel genes for atopy included SIGLEC8 (p=8.07×10 −13 ), SLC29A1 (p=7.07×10 −12 ), and SMPD3 (p=1.48×10 −11 ). Expression quantitative trait locus (eQTL) analyses identified multiple asthma-relevant genotype-expression pairs, such as rs2255888/ ALOX15 . Pathway enrichment analysis uncovered sixteen significantly enriched pathways at p We have identified genes and pathways for atopy and atopic asthma in children and adolescents, using transcriptome-wide data from white blood cells and whole blood samples.