Genome admixture analysis of 1,030 Ugandan infants with neonatal sepsis and hydrocephalus demonstrates geographical stratification of population disease risk.

Background: Neonatal disorders such as post-infectious hydrocephalus exhibit a higher incidence in Africa, where the intricate relationships between genetic ancestry, environmental exposures, and other risk factors likely contribute to the increased incidence. Methods: To start to characterize the common genetic architecture of Ugandan infants, we analyzed genome sequencing data from 1,030 Ugandan infants recruited from studies targeting neonatal sepsis and hydrocephalus. We employed genetic admixture analysis and integrated geospatial data to examine the relationships between genetic backgrounds and disease prevalence within this cohort. Results: Our results identified four distinct genetic admixture groups, each correlating strongly with specific geographic distributions across Uganda. Notably, a predominance of one admixture group, most common in northern Uganda, was overrepresented in the participants with post-infectious hydrocephalus. Conclusion: This study underscores the importance of genetic factors in disease manifestation at the population level, and a role for such precision public health approaches in complex neonatal disorders in African populations.