Dataset Information

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.

SUBMITTER: Parviainen R

PROVIDER: S-EPMC7388260 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Parviainen Roope R Skarp Sini S Korhonen Linda L Serlo Willy W Männikkö Minna M Sinikumpu Juha-Jaakko JJ

Experimental and therapeutic medicine 20200612 2

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 ...[more]

PMID: 32742401

Similar Datasets

Project description:Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged > 55 years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey–Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey–Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han–Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p < 5 × 10? 8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p = 4.6 × 10? 8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98–1.14; p = 0.17), displaying high degree of heterogeneity (I2 = 57%; Qhet p = 0.0006). Under Han–Eskin alternative random effects model the summary effect was significant (p = 0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size > 1.25) may still be consistent with an effect size < 1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets