PT  - JOURNAL ARTICLE
AU  - Pagé C. Goddard
AU  - Kevin L. Keys
AU  - Angel C.Y. Mak
AU  - Eunice Yujung Lee
AU  - Amy K. Liu
AU  - Lesly-Anne Samedy-Bates
AU  - Oona Risse-Adams
AU  - María G. Contreras
AU  - Jennifer R. Elhawary
AU  - Donglei Hu
AU  - Scott Huntsman
AU  - Sam S. Oh
AU  - Sandra Salazar
AU  - Celeste Eng
AU  - Blanca E. Himes
AU  - Marquitta J. White
AU  - Esteban G. Burchard
TI  - Integrative genomic analysis in African American children with asthma finds 3 novel loci associated with lung function
AID  - 10.1101/2020.05.01.045468
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.05.01.045468
4099  - http://biorxiv.org/content/early/2020/05/03/2020.05.01.045468.short
4100  - http://biorxiv.org/content/early/2020/05/03/2020.05.01.045468.full
AB  - Bronchodilator drugs are commonly prescribed for treatment and management of obstructive lung function present with diseases such as asthma. Administration of bronchodilator medication can partially or fully restore lung function as measured by pulmonary function tests. The genetics of baseline lung function measures taken prior to bronchodilator medication has been extensively studied, and the genetics of the bronchodilator response itself has received some attention. However, few studies have focused on the genetics of post-bronchodilator lung function. To address this gap, we analyzed lung function phenotypes in 1,103 subjects from the Study of African Americans, Asthma, Genes, and Environment (SAGE), 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 (FEV1, FVC, and FEV1/FVC) taken before and after albuterol bronchodilator administration on the same subjects, yielding six traits. We identified 18 GWAS loci, and 5 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-bronchodilator lung function: ADAMTS1, RAD54B, and EGLN3.Competing Interest StatementThe authors have declared no competing interest.