María G Contreras1,2,3, Kevin Keys1, Joaquin Magaña1, Pagé C Goddard1, Oona Risse-Adams1,4, Andrew M Zeiger1,5, Angel C Y Mak1, Lesly-Anne Samedy-Bates1,6, Andreas M Neophytou7,8, Eunice Lee9, Neeta Thakur1, Jennifer R Elhawary1, Donglei Hu1, Scott Huntsman1, Celeste Eng1, Ting Hu10, Esteban G Burchard1,6, Marquitta J White1. 1. Department of Medicine, University of California, San Francisco, CA. 2. SF BUILD, San Francisco State University, San Francisco, CA. 3. MARC, San Francisco State University, San Francisco, CA. 4. Lowell Science Research Program, Lowell High School, San Francisco, CA. 5. Department of Biology, University of Washington, Seattle, WA. 6. Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA. 7. Environmental Health Sciences Division, Berkeley School of Public Health, Berkeley, CA. 8. Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO. 9. National Institute of Environmental Health Sciences, Cary NC. 10. School of Computing, Queen's University, Kingston, ON, Canada.
Abstract
Objective: Asthma is the most common chronic disease in children. Short-acting bronchodilator medications are the most commonly prescribed asthma treatment worldwide, regardless of disease severity. Puerto Rican children display the highest asthma morbidity and mortality of any US population. Alarmingly, Puerto Rican children with asthma display poor bronchodilator drug response (BDR). Reduced BDR may explain, in part, the increased asthma morbidity and mortality observed in Puerto Rican children with asthma. Gene-environment interactions may explain a portion of the heritability of BDR. We aimed to identify gene-environment interactions associated with BDR in Puerto Rican children with asthma. Setting: Genetic, environmental, and psycho-social data from the Genes-environments and Admixture in Latino Americans (GALA II) case-control study. Participants: Our discovery dataset consisted of 658 Puerto Rican children with asthma; our replication dataset consisted of 514 Mexican American children with asthma. Main Outcome Measures: We assessed the association of pairwise interaction models with BDR using ViSEN (Visualization of Statistical Epistasis Networks). Results: We identified a non-linear interaction between Native American genetic ancestry and air pollution significantly associated with BDR in Puerto Rican children with asthma. This interaction was robust to adjustment for age and sex but was not significantly associated with BDR in our replication population. Conclusions: Decreased Native American ancestry coupled with increased air pollution exposure was associated with increased BDR in Puerto Rican children with asthma. Our study acknowledges BDR's phenotypic complexity, and emphasizes the importance of integrating social, environmental, and biological data to further our understanding of complex disease.
Objective: Asthma is the most common chronic disease in children. Short-acting bronchodilator medications are the most commonly prescribed asthma treatment worldwide, regardless of disease severity. Puerto Rican children display the highest asthma morbidity and mortality of any US population. Alarmingly, Puerto Rican children with asthma display poor bronchodilator drug response (BDR). Reduced BDR may explain, in part, the increased asthma morbidity and mortality observed in Puerto Rican children with asthma. Gene-environment interactions may explain a portion of the heritability of BDR. We aimed to identify gene-environment interactions associated with BDR in Puerto Rican children with asthma. Setting: Genetic, environmental, and psycho-social data from the Genes-environments and Admixture in Latino Americans (GALA II) case-control study. Participants: Our discovery dataset consisted of 658 Puerto Rican children with asthma; our replication dataset consisted of 514 Mexican American children with asthma. Main Outcome Measures: We assessed the association of pairwise interaction models with BDR using ViSEN (Visualization of Statistical Epistasis Networks). Results: We identified a non-linear interaction between Native American genetic ancestry and air pollution significantly associated with BDR in Puerto Rican children with asthma. This interaction was robust to adjustment for age and sex but was not significantly associated with BDR in our replication population. Conclusions: Decreased Native American ancestry coupled with increased air pollution exposure was associated with increased BDR in Puerto Rican children with asthma. Our study acknowledges BDR's phenotypic complexity, and emphasizes the importance of integrating social, environmental, and biological data to further our understanding of complex disease.
Authors: Katherine A Drake; Dara G Torgerson; Christopher R Gignoux; Joshua M Galanter; Lindsey A Roth; Scott Huntsman; Celeste Eng; Sam S Oh; Sook Wah Yee; Lawrence Lin; Carlos D Bustamante; Andrés Moreno-Estrada; Karla Sandoval; Adam Davis; Luisa N Borrell; Harold J Farber; Rajesh Kumar; Pedro C Avila; Emerita Brigino-Buenaventura; Rocio Chapela; Jean G Ford; Michael A Lenoir; Fred Lurmann; Kelley Meade; Denise Serebrisky; Shannon Thyne; William Rodríguez-Cintrón; Saunak Sen; José R Rodríguez-Santana; Ryan D Hernandez; Kathleen M Giacomini; Esteban G Burchard Journal: J Allergy Clin Immunol Date: 2013-08-29 Impact factor: 10.793
Authors: Andrea M Coverstone; Leonard B Bacharier; Bradley S Wilson; Anne M Fitzpatrick; William Gerald Teague; Wanda Phipatanakul; Sally E Wenzel; Benjamin M Gaston; Eugene R Bleecker; Wendy C Moore; Sima Ramratnam; Nizar N Jarjour; Ngoc P Ly; John V Fahy; David T Mauger; Kenneth B Schechtman; Huiqing Yin-DeClue; Jonathan S Boomer; Mario Castro Journal: Pediatr Pulmonol Date: 2019-08-19
Authors: Neeta Thakur; Nicolas E Barcelo; Luisa N Borrell; Smriti Singh; Celeste Eng; Adam Davis; Kelley Meade; Michael A LeNoir; Pedro C Avila; Harold J Farber; Denise Serebrisky; Emerita Brigino-Buenaventura; William Rodriguez-Cintron; Shannon Thyne; Jose R Rodriguez-Santana; Saunak Sen; Kirsten Bibbins-Domingo; Esteban Gonzalez Burchard Journal: Chest Date: 2016-12-01 Impact factor: 9.410
Authors: R Graham Barr; Larissa Avilés-Santa; Sonia M Davis; Tom K Aldrich; Franklyn Gonzalez; Ashley G Henderson; Robert C Kaplan; Lisa LaVange; Kiang Liu; Jose S Loredo; Eliana S Mendes; Ai Ni; Andrew Ries; Matthias Salathe; Lewis J Smith Journal: Am J Respir Crit Care Med Date: 2016-02-15 Impact factor: 21.405
Authors: Maria Pino-Yanes; Neeta Thakur; Christopher R Gignoux; Joshua M Galanter; Lindsey A Roth; Celeste Eng; Katherine K Nishimura; Sam S Oh; Hita Vora; Scott Huntsman; Elizabeth A Nguyen; Donglei Hu; Katherine A Drake; David V Conti; Andres Moreno-Estrada; Karla Sandoval; Cheryl A Winkler; Luisa N Borrell; Fred Lurmann; Talat S Islam; Adam Davis; Harold J Farber; Kelley Meade; Pedro C Avila; Denise Serebrisky; Kirsten Bibbins-Domingo; Michael A Lenoir; Jean G Ford; Emerita Brigino-Buenaventura; William Rodriguez-Cintron; Shannon M Thyne; Saunak Sen; Jose R Rodriguez-Santana; Carlos D Bustamante; L Keoki Williams; Frank D Gilliland; W James Gauderman; Rajesh Kumar; Dara G Torgerson; Esteban G Burchard Journal: J Allergy Clin Immunol Date: 2014-10-06 Impact factor: 10.793