A single genetic locus associated with pediatric fractures:a genome-wide association study on 3,230 patients

Abstract The understanding of the biological and environmental risk factors of fractures in pediatrics is limited. Previous studies have reported that fractures involve heritable traits, but the genetic factors contributing to the risk of fractures remain elusive. Furthermore, genetic influences specific to immature bone have not been thoroughly studied. Therefore, the aim of the present study was to identify genetic variations that are associated with fractures in early childhood. The present study used a prospective Northern Finland Birth Cohort (year 1986; n=9,432). The study population was comprised of 3,230 cohort members with available genotype data. A total of 48 members of the cohort (1.5%) had in‑hospital treated bone fractures during their first 6 years of life. Furthermore, individuals without fracture (n=3,182) were used as controls. A genome‑wide association study (GWAS) was performed using a frequentist association test. In the GWAS analysis, a linear regression model was fitted to test for additive effects of single‑nucleotide polymorphisms (SNPs; genotype dosage) adjusting for sex and performing population stratification using genotypic principal components. Using the GWAS analysis, the present study identified one locus with a significant association with fractures during childhood on chromosome 10 (rs112635931) and six loci with a suggested implication. The lead SNP rs112635931 was located near proline‑ and serine‑rich 2 (PROSER2) antisense RNA 1 (PROSER2‑AS1) and PROSER2, thus suggesting that these may be novel candidate genes associated with the risk of pediatric fractures