Lung Function in African American Children with Asthma Is Associated with Novel Regulatory Variants of the KIT Ligand KITLG/SCF and Gene-By-Air-Pollution Interaction

摘要: Baseline lung function, quantified as forced expiratory volume in the first second of exhalation (FEV1), is a standard diagnostic criterion used by clinicians to identify and classify diseases. Using whole-genome sequencing data from National Heart, Lung, Blood Institute Trans-Omics for Precision Medicine project, we identified novel genetic association with FEV1 on chromosome 12 867 African American children asthma (P = 1.26 × 10-8, β 0.302). Conditional analysis within 1 Mb tag signal (rs73429450) yielded one major two other weaker independent signals this peak. We explored statistical functional evidence all variants linkage disequilibrium three nine most likely candidates responsible Hi-C expression QTL demonstrated that these physically interacted KITLG (KIT ligand, also known SCF), their minor alleles were associated increased gene nasal epithelial cells. Gene-by-air-pollution interaction found candidate variant rs58475486 past-year ambient sulfur dioxide exposure 0.003, 0.32). This study protective FEV1, possibly mediated through KITLG, asthma. has between function which established role orchestrating allergic inflammation