Identifying the Genetic Ancestry of the Pediatric Obesity-related Asthma Variant (rs6494395) at RPS27L

Obesity-related asthma (OA) is a severe asthma endotype that disproportionately affects children from minority ethnic groups. We previously identified downregulation of RPS27L (40S ribosomal protein S27-like) in CD4+ (T-helper) cells from children with OA compared to cells from healthy-weight asthma (HwA) that was associated with the C allele at rs6494395 locus. In keeping with elevated allele frequencies in populations with Latino and African ancestries, we found higher allele frequency of rs6494395 in Hispanic and African American children with OA. Therefore, we tested the hypothesis that rs6494395 is ancestry-specific. We performed global and local genomic ancestry analysis using the programs ADMIXTURE and RFMix, respectively, to characterize the genetic ancestry of the cohort and to identify the ancestry of the genomic region containing the variant rs6494395 in the same multi-ethnic pediatric cohort where the effect of the variant on obese-related asthma was discovered. Our results indicate that rs6494395 is of African genetic ancestry. Understanding the genetic underpinnings of pediatric OA in diverse populations can improve precision medicine approaches and address health disparities in asthma outcomes.