Genetic Ancestry Plays a Role in Asthma Risk

Jonathan Pham, MBBS, BPharm, MPH

Credit: University of Melbourne

The relationship between genetic ancestry and asthma risk, as well as the environmental factors that can modify or mediate associations, was discussed in a research letter written by Jonathan Pham, Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, School of Population & Global Health, The University of Melbourne, and a team of investigators.¹

The results indicated that Native American ancestry was associated with a lower risk of asthma while African-American populations had an increased risk of asthma with every 10% increase in African ancestry suggesting genetic ancestry can impact asthma risk.

Previous evidence exhibited this relationship can vary depending on the ethnic population and geographic origin, according to the letter.²

Associations of Ancestry and Asthma

The team conducted a systematic review of published studies on this topic and found specific ethnic populations have a higher prevalence of asthma, which can be independent of socioeconomic status.¹

Genetic ancestry may lead to disease via epigenetic mechanisms, such as DNA methylation, which can differ significantly between these groups depending on genetic and cultural/behavioral factors, as well as environmental factors like tobacco smoke, air pollution, and airborne pathogens.

The study identified 9 eligible manuscripts from 114 records, including 14 independent cohorts, with 7 of 9 focusing on African ancestry, followed by European (n= 6), Native American (n= 3), Asian (n= 1), and Iberian (n= 1) ancestries.

Most manuscripts (6 of 9) studied individuals residing in the US, while the remaining 3 investigated individuals living in Brazil, the Canary Islands, and Peru. No studies were assessed as having a significant risk of bias.

Relationship Between Genetic Ancestry and Asthma

In 3 of the manuscripts, Native American ancestry was associated with a lower risk of asthma. Investigators also observed self-identified African-American populations showed an increased risk of asthma with every 10% increase in African ancestry in 2 manuscripts with 3 different cohorts. Among self-identified Hispanic populations living in the US, African ancestry was associated with a nil-to-modestly increased asthma risk in 2 manuscripts with 3 different cohorts.

The review also identified possible effect modifiers for the relationship between genetic ancestry and asthma, such as cultural affiliation, country of residence, and socio-economic status.

These findings indicate vulnerability to asthma among certain populations as a result of a combination of genetic and sociodemographic factors, which induce gene-environment interactions between genetic ancestry, country of residence, cultural affiliation, and socioeconomic status.

Native American genetic ancestry was found to be protective from asthma, while other ancestries were not. Investigators wrote that migration could play a role in the association, as migrants to new environments may induce certain immunological processes.

The association between asthma and African genetic ancestry was found to be amplified among African Americans and in South America but lessened among Hispanic Americans and in Caribbean countries. The letter suggested this was an effect modification or mediation by environmental factors.

The association between genetic ancestry and asthma was also found to be stronger in high socioeconomic classes, possibly due to increased hygiene and reduced levels of protective microbiologic exposure in early life, according to the review.

The team recommended future research in this area to better understand the mechanisms underlying these associations and their implications for asthma prevention and treatment. They acknowledged that the paucity of genetic cohorts available, small sample sizes, and heterogeneity of findings were limitations of the review.

However, they emphasized these data support the important role of genetic ancestry in asthma risk. Future investigation should identify genetic targets for therapeutic intervention, catering to at-risk genetic profiles, in order to alleviate asthma inequality across ethnic populations. In addtion, the sociodemographic profiles identified in these results could be targeted for additional public health intervention.

References:

1. Pham, J., Bui, D.S., Lodge, C.J., Abramson, M.J., Lowe, A.J., Li, S., Win, A.K., Hew, M. and Dharmage, S.C. (2023), Genetic ancestry is associated with asthma, and this could be modified by environmental factors. A systematic review. Clin Exp Allergy. https://doi.org/10.1111/cea.14308
2. Pham J, Hew M, Dharmage SC. Is ethnicity a “treatable trait” in asthma? Respirology. 2021;26(6):529-531.