Integrative genomic analysis in African American children with asthma finds three novel loci associated with lung function.

TitleIntegrative genomic analysis in African American children with asthma finds three novel loci associated with lung function.
Publication TypeJournal Article
Year of Publication2020
AuthorsGoddard, PC, Keys, KL, C Y Mak, A, Lee, EY, Liu, AK, Samedy-Bates, L-A, Risse-Adams, O, Contreras, MG, Elhawary, JR, Hu, D, Huntsman, S, Oh, SS, Salazar, S, Eng, C, Himes, BE, White, MJ, Burchard, EG
JournalGenet Epidemiol
Date Published2020 Sep 29
ISSN1098-2272
Abstract

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.

DOI10.1002/gepi.22365
Alternate JournalGenet. Epidemiol.
PubMed ID32989782
Grant ListGBMF3834 / / Gordon and Betty Moore Foundation /
R01ES015794 / ES / NIEHS NIH HHS / United States
R21ES24844 / ES / NIEHS NIH HHS / United States
24RT-0025 / / Tobacco-Related Disease Research Program /
27IR-0030 / / Tobacco-Related Disease Research Program /
T32HG000044 / HG / NHGRI NIH HHS / United States
U01HG007419 / HG / NHGRI NIH HHS / United States
U01HG009080 / HG / NHGRI NIH HHS / United States
R01HD085993 / / Eunice Kennedy Shriver National Institute of Child Health and Human Development /
P60MD006902 / MD / NIMHD NIH HHS / United States
R01MD010443 / MD / NIMHD NIH HHS / United States
R56MD013312 / MD / NIMHD NIH HHS / United States
K01HL140218 / HL / NHLBI NIH HHS / United States
R01HL104608 / HL / NHLBI NIH HHS / United States
R01HL117004 / HL / NHLBI NIH HHS / United States
R01HL117004-S1 / HL / NHLBI NIH HHS / United States
R01HL128439 / HL / NHLBI NIH HHS / United States
R01HL135156 / HL / NHLBI NIH HHS / United States
R01HL135156-S1 / HL / NHLBI NIH HHS / United States
R01HL141845 / HL / NHLBI NIH HHS / United States
R01HL141992 / HL / NHLBI NIH HHS / United States
U01HL138626 / HL / NHLBI NIH HHS / United States
X01HL134589 / HL / NHLBI NIH HHS / United States
1UL1GM118985 / GM / NIGMS NIH HHS / United States
K12GM081266 / GM / NIGMS NIH HHS / United States
RL5GM118984 / GM / NIGMS NIH HHS / United States
T32GM007546 / GM / NIGMS NIH HHS / United States
TL4GM118986 / GM / NIGMS NIH HHS / United States
2013-10-27 / / Alfred P. Sloan Foundation /