The relationship between genetic ancestry and pediatric asthma readmission is largely mediated by social and environmental factors
Published: July 1, 2021
Genetic ancestry studies have predominately looked for direct biologic effects on disease. Effects of genetic ancestry may be largely mediated by structural racism and its effect on socioenvironmental factors. A recent study published in The Journal of Allergy and Clinical Immunology (JACI) sought to determine whether asthma-related readmissions differed by degree of African ancestry and the extent to which such an association would also be explained or mediated by socio-environmental risk factors.
Mersha et al. used data from a prospective cohort study of 695 self- or caregiver-identified Black and White children aged 1-16 years with an asthma-related admission. The primary outcome was a similar readmission within 12 months. Each subject’s African ancestry was determined by single nucleotide polymorphisms, on a continuous scale ranging from 0-1 (0=no African ancestry; 1=100% African ancestry). The study also assessed 37 social, environmental, and clinical variables that were clustered into six domains (e.g., hardship, disease management). Kaplan Meier estimates of survival curves and mediation analyses were conducted.
A total of 134 (19.3%) children were readmitted within 12 months. For every 10% increase in African ancestry, there was 1.11 fold higher in odds of asthma readmission within 12 months (1.05-1.18; 95% confidence interval) with adjustment for age and sex. The association between African ancestry and readmission was mediated by family hardship (standardized coefficient: sβ=3.42, p<0.001) and disease management (sβ=0.046, p=0.001), accounting for >50% of African ancestry’s effect on readmission. These results are consistent with the notion that asthma-related racial disparities are driven by factors like structural racism and social adversity.
Although an increase in African ancestry is associated with increased odds of asthma readmission, the mediation analysis suggests family hardships and poor disease management are the main reasons why children with higher African ancestry experience higher odds of readmissions. Importantly, there was no direct African ancestry effect on readmission after accounting for these mediating pathways which is consistent with the notion that asthma-related racial disparities are likely driven by factors linked to structural racism and social adversities. These results suggest that future studies of reported race, genetic ancestry, and health outcomes should include measurement of relevant social and environmental variables. Further, precision medicine studies based on genetic ancestry should strongly consider inclusion of social and environmental variables to assess genetic contributions most accurately. Moreover, precision medicine interventions may often need to target non-genetic social and environmental pathways.
The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.
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