Data from: Integrative genomic analysis in African American children with asthma finds 3 novel loci associated with lung function

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.