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