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Asthma-Linked Loci Uncovered in Genome-Wide Analysis of Individuals of African Ancestry

NEW YORK (GenomeWeb) – Researchers have uncovered genetic loci that could contribute to asthma risk among individuals of African ancestry.

Individuals of African ancestry have high rates of common, chronic conditions, including asthma. In the US, 11.6 percent of African-Americans have asthma, while 8.3 percent of whites do, according to the Centers for Disease Control and Prevention. While part of the risk may be due to environmental or socioeconomic factors, genetics is also thought to play a part.

A team led by University of Colorado Anschutz Medical Campus researchers conducted a genome-wide meta-analysis of 14,000 individuals of African ancestry through which it uncovered both known and novel loci associated with asthma risk. Two of the loci the researchers identified might be specific to individuals of African ancestry, as they reported in Nature Communications this week.

"We need to understand what is driving asthma in these populations," senior author Kathleen Barnes, the director of the Colorado Center for Personalized Medicine at CU Anschutz, said in a statement. "Now we have a much better genetic foundation for pursuing this."

As part of Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA), Barnes and her colleagues previously sequenced 650 individuals of African descent living in the Americas and in West Africa. They used that data to develop a SNP genotyping chip in collaboration with Illumina, dubbed the African Diaspora Power Chip (ADPC), which has also been folded into Illumina's Multi-Ethnic Global Array (MEGA).

In their new study, the researchers used the ADPC array to genotype CAAPA participants from nine studies, including ones of African-American, Barbadian, and Puerto Rican individuals, and the MEGA array to genotype additional asthma studies of African-American, South American, and Caribbean individuals. In all, their analysis included 7,009 individuals with asthma and 7,645 controls, with varying levels of African genetic ancestry.

Four of the loci that reached genome-wide significance in the researchers' analysis had previously been uncovered in studies based on primarily individuals of European descent. This included the 17q12-q21 chromosomal region, which the researchers noted has been strongly linked to asthma risk.

However, the researchers added that the link between this region and asthma among individuals of African ancestry had a smaller effect size, as compared to individuals of other ancestries.

Other associations the researchers found were novel. They identified, for instance, a link between a gene on chromosome 8p23 that encodes a long non-coding RNA and asthma. Further long-range chromatin interaction and expression analyses implicated two genes, ARHGEF10 and MYOM2, that could account for the association, as ARHGEF10 has been linked to chronic obstructive pulmonary disorder and MYOM2 to lung function. However, the researchers noted this association was not captured by other asthma studies and they were unable to replicate it using summary statistics from the Trans-National Asthma Genetic Consortium.

They also identified three other novel loci, all of which were low-frequency variants. One at 8q24, though, was intronic to the TATDN1 gene, which is expressed in human airway smooth muscle cells stimulated with interleukin 17A, though it did not replicate in other studies.

The researchers were unable to replicate the 8p23 or 8q24 associations — which they noted could be in part due to the other studies' designs as some focused more on cardiovascular disease — but they said they could represent asthma risk-linked loci specific to African ancestry populations, although more research is needed.

"Ultimately, we hope that a better understanding of the genetic risk factors for asthma in African ancestry populations will lead to the development of better therapeutic interventions," first author Michelle Daya, an assistant professor at the CU School of Medicine, said in a statement.

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