Journal Article

S-PrediXcan predicted gene expression in human placenta is associated with childhood-onset asthma risk

Schoettler, Nathan, Snyder, Brittney M., Ober, Carole, McKennan, Christopher G., Hellwege, Jacklyn N., Jasper, Elizabeth A., Thompson, Emma E., Gebretsadik, Tebeb, Edwards, Todd L., Hartert, Tina V., Velez Edwards, Digna R.

2026

Overview

Investigation of in utero , tissue-specific molecular pathways contributing to prenatal programming of childhood-onset asthma is needed to develop effective, targeted prevention strategies. We aimed to examine the relationship between predicted gene expression in placenta and childhood-onset asthma and to compare relationships between childhood- and adult-onset asthma. Asthma genome-wide association study published summary statistics were obtained from the UK Biobank and published placental gene expression quantitative trait loci were obtained from the Rhode Island Child Health Study. We used S-PrediXcan to evaluate and compare associations between placental predicted gene expression and childhood- and adult-onset asthma and to determine whether signals were placenta-specific. Among 8,038 tested placental predicted expression-asthma associations, we identified 56 (0.7%) genes only significantly associated with childhood-onset asthma, 12 (0.1%) genes only significantly associated with adult-onset asthma, and 18 (0.2%) shared genes. Predicted expression of several genes ( ACTL9 , AMN , C9orf38 , C11orf30 , CTSE , EFCAB13 , EIF4E1B , FN1 , GLS2 , IL6 , IVL , LZIC , MAN2A2 , MEGT1 , RACGAP1 , SMAD6 , SPATA5 , TMEM25 , VTI1B , WDR19 ) was not significantly associated with childhood- or adult-onset asthma in any non-placental tissue, suggesting that the associations may be placenta-specific. This study identified alterations in predicted expression of placental genes associated with transcriptional pathways critical to the development of asthma. We identified unique and shared pathways, particularly related to immune regulation, associated with childhood- and adult-onset. This expands our understanding of the fetal origins of asthma, highlights the placenta as an informative tissue in understanding asthma pathogenesis, and identifies target genes to prioritize for future functional studies.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/208/199 / 692/308/174 / 692/699/1785/31 / Adult / Age of Onset / Asthma / Asthma - epidemiology / Asthma - genetics / Asthma - metabolism / Child / Childhood / Children / Chronic illnesses / Chronic obstructive pulmonary disease / Disease prevention / Female / Fetuses / Gene Expression / Gene mapping / Genetic Predisposition to Disease / Genome-wide association studies / Genome-Wide Association Study / Genomes / Genotype & phenotype / Health risks / Humanities and Social Sciences / Humans / Immunoregulation / Male / multidisciplinary / Placenta / Placenta - metabolism / Polymorphism, Single Nucleotide / Pregnancy / Quantitative Trait Loci / Science / Science (multidisciplinary)