Genome-wide association study in minority children with asthma implicates DNAH5 in bronchodilator responsiveness
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 d...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-16488-6 |
| _version_ | 1818509815491592192 |
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| 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 |
| author_facet | 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 |
| author_sort | Jaehyun Joo |
| collection | DOAJ |
| description | 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 < 0.05). No genetic variant was associated with BDR at the genome-wide significant threshold in Mexicans and African Americans. Our findings help inform genetic underpinnings of BDR for understudied minority patients with asthma, but the limited availability of genetic data for racial/ethnic minority children with asthma remains a paramount challenge. |
| first_indexed | 2024-12-10T22:50:36Z |
| format | Article |
| id | doaj.art-808f2b5b81bf46269caaa117e076f965 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-10T22:50:36Z |
| publishDate | 2022-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-808f2b5b81bf46269caaa117e076f9652022-12-22T01:30:26ZengNature PortfolioScientific Reports2045-23222022-07-0112111110.1038/s41598-022-16488-6Genome-wide association study in minority children with asthma implicates DNAH5 in bronchodilator responsivenessJaehyun Joo0Angel C. Y. Mak1Shujie Xiao2Patrick M. Sleiman3Donglei Hu4Scott Huntsman5Celeste Eng6Mengyuan Kan7Avantika R. Diwakar8Jessica A. Lasky-Su9Scott T. Weiss10Joanne E. Sordillo11Ann C. Wu12Michelle Cloutier13Glorisa Canino14Erick Forno15Juan C. Celedón16Max A. Seibold17Hakon Hakonarson18L. Keoki Williams19Esteban G. Burchard20Blanca E. Himes21Department of Biostatistics, Epidemiology and Informatics, University of PennsylvaniaDepartment of Medicine, University of California, San Francisco, UCSFCenter for Individualized and Genomic Medicine Research, Department of Internal Medicine, Henry Ford Health SystemCenter for Applied Genomics, Children’s Hospital of PhiladelphiaDepartment of Medicine, University of California, San Francisco, UCSFDepartment of Medicine, University of California, San Francisco, UCSFDepartment of Medicine, University of California, San Francisco, UCSFDepartment of Biostatistics, Epidemiology and Informatics, University of PennsylvaniaDepartment of Biostatistics, Epidemiology and Informatics, University of PennsylvaniaDepartment of Medicine, Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical SchoolDepartment of Medicine, Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical SchoolPRecisiOn Medicine Translational Research (PROMoTeR) Center, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care InstitutePRecisiOn Medicine Translational Research (PROMoTeR) Center, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care InstituteDepartment of Pediatrics, University of ConnecticutBehavioral Sciences Research Institute, University of Puerto RicoDivision of Pediatric Pulmonary Medicine, UMPC Children’s Hospital of Pittsburgh, University of PittsburghDivision of Pediatric Pulmonary Medicine, UMPC Children’s Hospital of Pittsburgh, University of PittsburghCenter for Genes, Environment and Health, National Jewish HealthCenter for Applied Genomics, Children’s Hospital of PhiladelphiaCenter for Individualized and Genomic Medicine Research, Department of Internal Medicine, Henry Ford Health SystemDepartment of Medicine, University of California, San Francisco, UCSFDepartment of Biostatistics, Epidemiology and Informatics, University of PennsylvaniaAbstract 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 < 0.05). No genetic variant was associated with BDR at the genome-wide significant threshold in Mexicans and African Americans. Our findings help inform genetic underpinnings of BDR for understudied minority patients with asthma, but the limited availability of genetic data for racial/ethnic minority children with asthma remains a paramount challenge.https://doi.org/10.1038/s41598-022-16488-6 |
| spellingShingle | 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 Genome-wide association study in minority children with asthma implicates DNAH5 in bronchodilator responsiveness Scientific Reports |
| title | Genome-wide association study in minority children with asthma implicates DNAH5 in bronchodilator responsiveness |
| title_full | Genome-wide association study in minority children with asthma implicates DNAH5 in bronchodilator responsiveness |
| title_fullStr | Genome-wide association study in minority children with asthma implicates DNAH5 in bronchodilator responsiveness |
| title_full_unstemmed | Genome-wide association study in minority children with asthma implicates DNAH5 in bronchodilator responsiveness |
| title_short | Genome-wide association study in minority children with asthma implicates DNAH5 in bronchodilator responsiveness |
| title_sort | genome wide association study in minority children with asthma implicates dnah5 in bronchodilator responsiveness |
| url | https://doi.org/10.1038/s41598-022-16488-6 |
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