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Meta-Analysis
. 2023 Apr;151(4):1132-1136.
doi: 10.1016/j.jaci.2022.09.001. Epub 2022 Sep 8.

Genetic architecture of asthma in African American patients

Xiao Chang  1 , Michael March  2 , Frank Mentch  2 , Huiqi Qu  2 , Yichuan Liu  2 , Joseph Glessner  2 , Patrick Sleiman  3 , Hakon Hakonarson  4
Affiliations
Meta-Analysis

Genetic architecture of asthma in African American patients

Xiao Chang et al. J Allergy Clin Immunol. 2023 Apr.

Abstract

Background: 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.

Objective: We aimed to identify genetic loci associated with asthma in African American individuals.

Methods: 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.

Results: 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).

Conclusions: Our findings provide candidate genetic loci for therapeutic target identification and prioritization for African populations.

Keywords: African American individuals; Asthma; GWAS.

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Conflict of interest statement

Conflicts of interest

The authors declare that they have no conflict of interest.

Figures

Fig 1.
Fig 1.
Manhattan plot of the GWAS meta-analysis of the CHOP and CAAPA cohorts. Loci passing significant threshold (3 × 10−8) are colored in blue and loci passing significant threshold (5 × 10−8) are colored in yellow.
See this image and copyright information in PMC

Comment in

References

    1. Han Y, Jia Q, Jahani PS, Hurrell BP, Pan C, Huang P, et al. Genome-wide analysis highlights contribution of immune system pathways to the genetic architecture of asthma. Nat Commun 2020; 11:1776. - PMC - PubMed
    1. Daya M, Rafaels N, Brunetti TM, Chavan S, Levin AM, Shetty A, et al. Association study in African-admixed populations across the Americas recapitulates asthma risk loci in non-African populations. Nat Commun 2019; 10:880. - PMC - PubMed
    1. Almoguera B, Vazquez L, Mentch F, Connolly J, Pacheco JA, Sundaresan AS, et al. Identification of Four Novel Loci in Asthma in European American and African American Populations. Am J Respir Crit Care Med 2017; 195:456–63. - PMC - PubMed
    1. Das S, Forer L, Schonherr S, Sidore C, Locke AE, Kwong A, et al. Next-generation genotype imputation service and methods. Nat Genet 2016; 48:1284–7. - PMC - PubMed
    1. Willer CJ, Li Y, Abecasis GR. METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics 2010; 26:2190–1. - PMC - PubMed

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