%0 Journal Article %J J Allergy Clin Immunol %D 2021 %T A deoxyribonuclease 1-like 3 genetic variant associates with asthma exacerbations. %A Herrera-Luis, Esther %A Lorenzo-Diaz, Fabian %A Samedy-Bates, Lesly-Anne %A Eng, Celeste %A Villar, Jesús %A Rodriguez-Santana, Jose R %A Burchard, Esteban G %A Pino-Yanes, Maria %B J Allergy Clin Immunol %V 147 %P 1095-1097.e10 %8 2021 Mar %G eng %N 3 %1 https://www.ncbi.nlm.nih.gov/pubmed/33035569?dopt=Abstract %R 10.1016/j.jaci.2020.09.027 %0 Journal Article %J Genet Epidemiol %D 2021 %T Integrative genomic analysis in African American children with asthma finds three novel loci associated with lung function. %A Goddard, Pagé C %A Keys, Kevin L %A Mak, Angel C Y %A Lee, Eunice Y %A Liu, Amy K %A Samedy-Bates, Lesly-Anne %A Risse-Adams, Oona %A Contreras, María G %A Elhawary, Jennifer R %A Hu, Donglei %A Huntsman, Scott %A Oh, Sam S %A Salazar, Sandra %A Eng, Celeste %A Himes, Blanca E %A White, Marquitta J %A Burchard, Esteban G %X

Bronchodilator (BD) drugs are commonly prescribed for treatment and management of obstructive lung function present with diseases such as asthma. Administration of BD medication can partially or fully restore lung function as measured by pulmonary function tests. The genetics of baseline lung function measures taken before BD medication have been extensively studied, and the genetics of the BD response itself have received some attention. However, few studies have focused on the genetics of post-BD lung function. To address this gap, we analyzed lung function phenotypes in 1103 subjects from the Study of African Americans, Asthma, Genes, and Environment, a pediatric asthma case-control cohort, using an integrative genomic analysis approach that combined genotype, locus-specific genetic ancestry, and functional annotation information. We integrated genome-wide association study (GWAS) results with an admixture mapping scan of three pulmonary function tests (forced expiratory volume in 1 s [FEV ], forced vital capacity [FVC], and FEV /FVC) taken before and after albuterol BD administration on the same subjects, yielding six traits. We identified 18 GWAS loci, and five additional loci from admixture mapping, spanning several known and novel lung function candidate genes. Most loci identified via admixture mapping exhibited wide variation in minor allele frequency across genotyped global populations. Functional fine-mapping revealed an enrichment of epigenetic annotations from peripheral blood mononuclear cells, fetal lung tissue, and lung fibroblasts. Our results point to three novel potential genetic drivers of pre- and post-BD lung function: ADAMTS1, RAD54B, and EGLN3.

%B Genet Epidemiol %V 45 %P 190-208 %8 2021 Mar %G eng %N 2 %1 https://www.ncbi.nlm.nih.gov/pubmed/32989782?dopt=Abstract %R 10.1002/gepi.22365 %0 Journal Article %J Ethn Dis %D 2021 %T Native American Ancestry and Air Pollution Interact to Impact Bronchodilator Response in Puerto Rican Children with Asthma. %A Contreras, María G %A Keys, Kevin %A Magaña, Joaquin %A Goddard, Pagé C %A Risse-Adams, Oona %A Zeiger, Andrew M %A Mak, Angel C Y %A Samedy-Bates, Lesly-Anne %A Neophytou, Andreas M %A Lee, Eunice %A Thakur, Neeta %A Elhawary, Jennifer R %A Hu, Donglei %A Huntsman, Scott %A Eng, Celeste %A Hu, Ting %A Burchard, Esteban G %A White, Marquitta J %X

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.

%B Ethn Dis %V 31 %P 77-88 %8 2021 Winter %G eng %N 1 %1 https://www.ncbi.nlm.nih.gov/pubmed/33519158?dopt=Abstract %R 10.18865/ed.31.1.77