Compositional analysis of genetic ancestry shows that relative proportion of African ancestry is positively associated with fecal myeloperoxidase in Brazilian infants
Year: 2026
Type: preprint
Study design: Observational Study
Abstract: Genetic ancestry composition has been used extensively as a predictor of clinical outcomes, multiomic biomarkers, and endophenotypes, but the models have most often used untransformed ancestry fractions as explanatory variables. Under a simplex constraint results from this type of model can be uninterpretable and misleading. We demonstrate the use of multiple transformed log ratio coordinates of ancestral proportions as predictors in a study of excreted myeloperoxidase (MPO), a neutrophilic enzyme used as a fecal biomarker to measure intestinal inflammation and enteropathy. We show how to convert these difficult-to-interpret effects into association results for shifts between two ancestries under an isoancestry constraint (holding an ancestry fraction constant) using post-estimation average marginal effects and explain their geometric interpretation. We found that increasing proportion of African ancestry was associated with increased levels of excreted MPO in low-income household infants in three Northeastern Brazil studies, with a smaller negative secondary association of European ancestry, all under a tri-continental ancestry composition (African, European, Amerindian). While the maximum log(MPO) outcome variance explained by differences in genetic ancestry was modest at a few percent, we show evidence that these differences in heritability were context-dependent on measurement of MPO under active enteric infection. The results were attenuated by socio-economic status, but a signal remained. Overall, we found that African genomes carry additional alleles that enable a more intensive neutrophil response to enteric infection relative to European and Amerindian genomes, illuminating a possible host genetic background role in modulating immune response to enteric diseases and pathogens.
Source: medRxiv
Institutions: University of Virginia, Universidade Federal do Ceará
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: University of Virginia - to apply highly sensitive quantitative molecular diagnostics for pathogens to understand the etiology of community diarrhea and the relationship an..., Fogarty International Center - to support data management, analysis, and publication of scientific results associated with the 0-24 month and 25-60 month cohort data collected fr..., Long term Impact and Intervention for Diarrhea in Brazil, G4314653862, University of Virginia - to identify why oral poliovirus and rotavirus vaccines are less effective in the developing world, in order to develop new approaches to protect ch..., G6548492370, G6907134380, Foundation for the National Institutes of Health (FNIH) - to determine the impact of enteric infections/diarrhea that alter gut function and impair children's nutrition, growth and development in order to ...
OpenAlex ID: W7220467260