학술논문
Genome-wide association study in minority children with asthma implicates DNAH5 in bronchodilator responsiveness
Document Type
article
Author
Jaehyun Joo; Angel C. Y. Mak; Shujie Xiao; Patrick M. Sleiman; Donglei Hu; Scott Huntsman; Celeste Eng; Mengyuan Kan; Avantika R. Diwakar; Jessica A. Lasky-Su; Scott T. Weiss; Joanne E. Sordillo; Ann C. Wu; Michelle Cloutier; Glorisa Canino; Erick Forno; Juan C. Celedón; Max A. Seibold; Hakon Hakonarson; L. Keoki Williams; Esteban G. Burchard; Blanca E. Himes
Source
Scientific Reports, Vol 12, Iss 1, Pp 1-11 (2022)
Subject
Language
English
ISSN
2045-2322
Abstract
Abstract Variability in response to short-acting β2-agonists (e.g., albuterol) among patients with asthma from diverse racial/ethnic groups may contribute to asthma disparities. We sought to identify genetic variants associated with bronchodilator response (BDR) to identify potential mechanisms of drug response and risk factors for worse asthma outcomes. Genome-wide association studies of bronchodilator response (BDR) were performed using TOPMed Whole Genome Sequencing data of the Asthma Translational Genomic Collaboration (ATGC), which corresponded to 1136 Puerto Rican, 656 Mexican and 4337 African American patients with asthma. With the population-specific GWAS results, a trans-ethnic meta-analysis was performed to identify BDR-associated variants shared across the three populations. Replication analysis was carried out in three pediatric asthma cohorts, including CAMP (Childhood Asthma Management Program; n = 560), GACRS (Genetics of Asthma in Costa Rica Study; n = 967) and HPR (Hartford-Puerto Rico; n = 417). A genome-wide significant locus (rs35661809; P = 3.61 × 10–8) in LINC02220, a non-coding RNA gene, was identified in Puerto Ricans. While this region was devoid of protein-coding genes, capture Hi-C data showed a distal interaction with the promoter of the DNAH5 gene in lung tissue. In replication analysis, the GACRS cohort yielded a nominal association (1-tailed P