Genetic architecture of asthma in African American patients

• Published in: Journal of allergy and clinical immunology Vol. 151; no. 4; pp. 1132 - 1136
• Main Authors: Chang, Xiao, March, Michael, Mentch, Frank, Qu, Huiqi, Liu, Yichuan, Glessner, Joseph, Sleiman, Patrick, Hakonarson, Hakon
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2023
• Subjects: African American individuals; Asthma; Asthma - genetics; Black or African American - genetics; Child; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; GWAS; Humans; Polymorphism, Single Nucleotide; Proteins - genetics; Quantitative Trait Loci; Short Chain Dehydrogenase-Reductases - genetics; African American individuals; GWAS; SNP; LD; CHOP; CAAPA; eQTL; Asthma
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2022.09.001

Asthma is a chronic inflammatory disorder with a strong genetic inheritance. Although more than 100 loci were reported through the genome-wide association study of European populations, the genetic underpinning of asthma in African American individuals remains largely elusive. We aimed to identify genetic loci associated with asthma in African American individuals. Three cohorts were genotyped at the Children's Hospital of Philadelphia by using the Illumina single-nucleotide polymorphism array platform. Genotype imputation was performed by using the Trans-Omics for Precision Medicine (TOPMed) reference panel, which includes whole genome sequencing data from more than 100,000 individuals. A meta-analysis of 3 Children's Hospital of Philadelphia cohorts and 10 Consortium on Asthma among African Ancestry Populations in the Americas cohorts, totaling 19,628 subjects, was conducted to identify genetic loci associated with asthma in African American individuals. Our study identified 12 loci surpassing the classical genome-wide significance threshold (5 × 10–8). Of those loci, 8 reached the stricter significance threshold (3 × 10–8). The 9p24.1 locus (rs10975467 [P = 1.63 × 10–8]) has previously been associated with asthma in European individuals. Six loci are associated with enhancer activities, 2 loci are in DNase I–hypersensitive regions, and all of them are associated with regulatory motifs. Moreover, the locus 11q13.4 (rs7480008) is an expression quantitative trait locus of XRRA1 in lung (P = 9.4 × 10–10), and the locus 13q14.3 (rs1543525) is a splicing quantitative trait locus of DHRS12 in lung (P = 1.1 × 10–13). Our findings provide candidate genetic loci for therapeutic target identification and prioritization for African populations.