Identification of novel loci in obstructive sleep apnea in European American and African American children

Abstract Study Objectives To identify genetic susceptibility variants in pediatric obstructive sleep apnea in European American and African American children. Methods A phenotyping algorithm using electronic medical records was developed to recruit cases with OSA and control subjects from the Center for Applied Genomics at Children’s Hospital of Philadelphia (CHOP). Genome-wide association studies (GWAS) were performed in pediatric OSA cases and control subjects with European American (EA) and African American (AA) ancestry followed by meta-analysis and sex stratification. Results The algorithm accrued 1486 subjects (46.3% European American, 53.7% African American). We identified genomic loci at 1p36.22 and 15q26.1 that associated with OSA risk in EA and AA, respectively. We also revealed a shared risk locus at 18p11.32 (rs114124196, p = 1.72 × 10-8) across EA and AA populations. Additionally, association at 1q43 (rs12754698) and 2p25.1 (rs72775219) was identified in the male-only analysis of EA children with OSA, while association at 8q21.11 (rs6472959), 11q24.3 (rs4370952) and 15q21.1 (rs149936782) was detected in the female-only analysis of EA children and association at 18p11.23 (rs9964029) was identified in the female-only analysis of African-American children. Moreover, the 18p11.32 locus was replicated in an EA cohort (rs114124196, p = 8.8 × 10-3). Conclusions We report the first GWAS for pediatric OSA in European Americans and African Americans. Our results provide novel insights to the genetic underpins of pediatric OSA.