A study published today in The Lancet Respiratory Medicine journal sheds light on the most common genetic region associated with childhood-onset asthma in African Americans.
“While people of African ancestry tend to have more asthma and more severe asthma than people of European ancestry, studies of genetic risk factors for childhood-onset asthma in African Americans have been inconclusive,” said lead author Carole Ober, PhD, professor and chairman of human genetics at the University of Chicago.
An associated region on chromosome 17 is very large and contains many genes, making it difficult to pinpoint specific genetic variants and specific genes that contribute to asthma risk. In previous studies in Europeans, all the single nucleotide polymorphisms (SNPs) across this region are associated with asthma and with the expression of the same gene or genes. The effects of different SNPs on gene expression, which can differ between tissues, can’t be separated.
The new study addressed these two challenges by focusing on African Americans and on gene expression in multiple tissues that are relevant to asthma: blood immune cells, upper airway (nasal) epithelial cells and lower airway (lung) epithelial cells. Because chromosomes of African ancestry are older than those of European ancestry, the pieces of chromosomes harboring SNPs associated with diseases are much smaller in African Americans.
The study shows SNPs associated with asthma in African Americans regulate the expression of the GSDMB gene in both upper and lower airway cells. In contrast, the SNPs regulating the expression of genes in blood cells are not central to asthma risk.
The researchers did a genetic association study and meta-analysis of the 17q12-21 SNPs for childhood-onset asthma in 5,916 European American and 3,904 African American children, which included children participants in birth cohorts from Children’s Respiratory and Environmental Workgroup (CREW), led by Dr. James Gern, professor and vice chair of research at the University of Wisconsin Department of Pediatrics. CREW is part of the National Institutes of Health (NIH) Environmental influences on Child Health Outcomes (ECHO) Program.
“If you look across the 17q region,” said Ober, “you find a lot of genotypes that are highly correlated in people of European origin. But in people of African and African American origin, the correlations between SNPs are much fewer. We were the first group to fine map this region in African Americans to find the variants and genes that underlie the association with childhood-onset asthma at this region.”
The study was funded by the NIH and is available to read in The Lancet Respiratory Medicine journal.