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
| Autor: | Max A. Seibold, Sandra Salazar, Zhanghua Chen, Soren Germer, Satria Sajuthi, Deepti Jain, Frank D. Gilliland, B. Saef, Jaehyun Joo, Esteban G. Burchard, Lara Heermans Winterkorn, Hakon Hakonarson, Marquitta J. White, Gonçalo R. Abecasis, Catherine Reeves, Ann Chen Wu, Shujie Xiao, Deborah A. Nickerson, Fred Lurmann, Scott Huntsman, Michael C. Zody, Patrick M. A. Sleiman, Celeste Eng, L. Keoki Williams, Kevin L. Keys, Eunice Y. Lee, Sam S. Oh, Hongsheng Gui, Angel C.Y. Mak, Donglei Hu, Hyun Min Kang, Rajesh Kumar, Elad Ziv, Blanca E. Himes, Fernando D. Martinez |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Linkage disequilibrium Adolescent FEV(1)gene-by-environment interaction air pollution Quantitative Trait Loci Genome-wide association study Biology Investigations Polymorphism Single Nucleotide Linkage Disequilibrium GxE 03 medical and health sciences Young Adult 0302 clinical medicine Forced Expiratory Volume medicine Genetics FEV1 gene-by-environment interaction GWAS Humans Allele African American Child Gene Chromosome 12 030304 developmental biology Genetic association Asthma Genetics of Complex Traits 0303 health sciences Stem Cell Factor Chromosomes Human Pair 12 SCF respiratory system medicine.disease respiratory tract diseases Black or African American Nasal Mucosa 030228 respiratory system KITLG Gene KITLG Female Gene-Environment Interaction Developmental Biology |
| Zdroj: | Genetics Genetics, vol 215, iss 3 |
| ISSN: | 1943-2631 0016-6731 |
| Popis: | Baseline lung function is a standard diagnostic criterion used by clinicians to detect lung diseases. It is a complex trait significantly influenced by both genetics and environmental factors... 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|