Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.


The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

Publication Detail

Title: 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.

Authors: Mak, Angel C Y; Sajuthi, Satria; Joo, Jaehyun; Xiao, Shujie; Sleiman, Patrick M; White, Marquitta J; Lee, Eunice Y; Saef, Benjamin; Hu, Donglei; Gui, Hongsheng; Keys, Kevin L; Lurmann, Fred; Jain, Deepti; Abecasis, Gonçalo; Kang, Hyun Min; Nickerson, Deborah A; Germer, Soren; Zody, Michael C; Winterkorn, Lara; Reeves, Catherine; Huntsman, Scott; Eng, Celeste; Salazar, Sandra; Oh, Sam S; Gilliland, Frank D; Chen, Zhanghua; Kumar, Rajesh; Martínez, Fernando D; Wu, Ann Chen; Ziv, Elad; Hakonarson, Hakon; Himes, Blanca E; Williams, L Keoki; Seibold, Max A; Burchard, Esteban G

Published In Genetics, (2020 07)

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

PubMed ID: 32327564 Exiting the NIEHS site

MeSH Terms: Adolescent; African Americans/genetics; Air Pollution*; Asthma/epidemiology; Asthma/genetics*; Asthma/physiopathology; Child; Chromosomes, Human, Pair 12/genetics; Female; Forced Expiratory Volume*; Gene-Environment Interaction*; Humans; Linkage Disequilibrium; Male; Nasal Mucosa/metabolism; Polymorphism, Single Nucleotide*; Quantitative Trait Loci*; Stem Cell Factor/genetics*; Stem Cell Factor/metabolism; Young Adult

to Top