Compositional analysis of genetic ancestry shows that relative proportion of African ancestry is positively associated with fecal myeloperoxidase in Brazilian infants
- 1University of Virginia
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.
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BibTeX
@misc{mychaleckyj2026compositional,
title = {{Compositional analysis of genetic ancestry shows that relative proportion of African ancestry is positively associated with fecal myeloperoxidase in Brazilian infants}},
author = {J. Mychaleckyj and A. Havt and U. Nayak and R. L. Guerrant and A. A. Lima},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.02.26364607},
url = {https://www.medrxiv.org/content/10.64898/2026.10.02.26364607v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Compositional analysis of genetic ancestry shows that relative proportion of African ancestry is positively associated with fecal myeloperoxidase in Brazilian infants
AU - J. Mychaleckyj
AU - A. Havt
AU - U. Nayak
AU - R. L. Guerrant
AU - A. A. Lima
PY - 2026
DA - 2026/10/02
PB - medRxiv
DO - 10.64898/2026.10.02.26364607
UR - https://www.medrxiv.org/content/10.64898/2026.10.02.26364607v1
AB - 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.
ER -