African-specific alleles modify risk for asthma at the 17q12-q21 locus in African Americans.
Genome Med
; 14(1): 112, 2022 09 29.
Article
in En
| MEDLINE
| ID: mdl-36175932
ABSTRACT
BACKGROUND:
Asthma is the most common chronic disease in children, occurring at higher frequencies and with more severe disease in children with African ancestry.METHODS:
We tested for association with haplotypes at the most replicated and significant childhood-onset asthma locus at 17q12-q21 and asthma in European American and African American children. Following this, we used whole-genome sequencing data from 1060 African American and 100 European American individuals to identify novel variants on a high-risk African American-specific haplotype. We characterized these variants in silico using gene expression and ATAC-seq data from airway epithelial cells, functional annotations from ENCODE, and promoter capture (pc)Hi-C maps in airway epithelial cells. Candidate causal variants were then assessed for correlation with asthma-associated phenotypes in African American children and adults.RESULTS:
Our studies revealed nine novel African-specific common variants, enriched on a high-risk asthma haplotype, which regulated the expression of GSDMA in airway epithelial cells and were associated with features of severe asthma. Using ENCODE annotations, ATAC-seq, and pcHi-C, we narrowed the associations to two candidate causal variants that are associated with features of T2 low severe asthma.CONCLUSIONS:
Previously unknown genetic variation at the 17q12-21 childhood-onset asthma locus contributes to asthma severity in individuals with African ancestries. We suggest that many other population-specific variants that have not been discovered in GWAS contribute to the genetic risk for asthma and other common diseases.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Asthma
/
Black or African American
Type of study:
Etiology_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Genome Med
Year:
2022
Document type:
Article
Affiliation country: