Tonsillar expression quantitative trait loci verify and expand genetic contributors to childhood atopic diseases.

Abstract

The spectrum of causal variants, mechanisms, and immunologic gene networks that influence pediatric atopic traits are not completely understood. Human genetic variation associated with transcript abundance (eQTLs) can help to advance our understanding, yet prior work has focused on profiling immune cell populations collected from peripheral blood primarily in adult populations, leaving uncharacterized tissue-resident lymphocytes collected from children. Characterize the gene expression of four populations of tonsil-derived immune cell-types collected from pediatric patients. Here, we collected naïve B, germinal center B, naïve T and T follicular helper cells from the discarded tonsils of 103 children across development (ages 1-19). We genotyped and RNA-sequenced these samples and performed differential expression and eQTL analysis, then statistically linked eQTL signals to relevant atopic traits via colocalization. We report differentially expressed genes across cell-types and identify 13,393 eGenes (1,793 eGenes not previously reported in similar datasets) influenced by 27,603 eQTLs (5,199 not previously reported). We link eQTLs to associations identified in pediatric and adult asthma and atopy traits, nominating 78 eGenes like TRAF3, ZBTB10 and JAZF1 in disease relevant cell-types. Our resource is freely available and exemplifies the importance of discovery in native tissues and across human development.