Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Parviainen, Roope, Skarp, Sini, Korhonen, Linda, Serlo, Willy, Männikkö, Minna, Sinikumpu, Juha-Jaakko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388260/
https://www.ncbi.nlm.nih.gov/pubmed/32742401
http://dx.doi.org/10.3892/etm.2020.8885
_version_ 1783564277060206592
author Parviainen, Roope
Skarp, Sini
Korhonen, Linda
Serlo, Willy
Männikkö, Minna
Sinikumpu, Juha-Jaakko
author_facet Parviainen, Roope
Skarp, Sini
Korhonen, Linda
Serlo, Willy
Männikkö, Minna
Sinikumpu, Juha-Jaakko
author_sort Parviainen, Roope
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7388260
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-73882602020-07-31 A single genetic locus associated with pediatric fractures: A genome-wide association study on 3,230 patients Parviainen, Roope Skarp, Sini Korhonen, Linda Serlo, Willy Männikkö, Minna Sinikumpu, Juha-Jaakko Exp Ther Med Articles 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. D.A. Spandidos 2020-08 2020-06-12 /pmc/articles/PMC7388260/ /pubmed/32742401 http://dx.doi.org/10.3892/etm.2020.8885 Text en Copyright: © Parviainen et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Parviainen, Roope
Skarp, Sini
Korhonen, Linda
Serlo, Willy
Männikkö, Minna
Sinikumpu, Juha-Jaakko
A single genetic locus associated with pediatric fractures: A genome-wide association study on 3,230 patients
title A single genetic locus associated with pediatric fractures: A genome-wide association study on 3,230 patients
title_full A single genetic locus associated with pediatric fractures: A genome-wide association study on 3,230 patients
title_fullStr A single genetic locus associated with pediatric fractures: A genome-wide association study on 3,230 patients
title_full_unstemmed A single genetic locus associated with pediatric fractures: A genome-wide association study on 3,230 patients
title_short A single genetic locus associated with pediatric fractures: A genome-wide association study on 3,230 patients
title_sort single genetic locus associated with pediatric fractures: a genome-wide association study on 3,230 patients
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388260/
https://www.ncbi.nlm.nih.gov/pubmed/32742401
http://dx.doi.org/10.3892/etm.2020.8885
work_keys_str_mv AT parviainenroope asinglegeneticlocusassociatedwithpediatricfracturesagenomewideassociationstudyon3230patients
AT skarpsini asinglegeneticlocusassociatedwithpediatricfracturesagenomewideassociationstudyon3230patients
AT korhonenlinda asinglegeneticlocusassociatedwithpediatricfracturesagenomewideassociationstudyon3230patients
AT serlowilly asinglegeneticlocusassociatedwithpediatricfracturesagenomewideassociationstudyon3230patients
AT mannikkominna asinglegeneticlocusassociatedwithpediatricfracturesagenomewideassociationstudyon3230patients
AT sinikumpujuhajaakko asinglegeneticlocusassociatedwithpediatricfracturesagenomewideassociationstudyon3230patients
AT parviainenroope singlegeneticlocusassociatedwithpediatricfracturesagenomewideassociationstudyon3230patients
AT skarpsini singlegeneticlocusassociatedwithpediatricfracturesagenomewideassociationstudyon3230patients
AT korhonenlinda singlegeneticlocusassociatedwithpediatricfracturesagenomewideassociationstudyon3230patients
AT serlowilly singlegeneticlocusassociatedwithpediatricfracturesagenomewideassociationstudyon3230patients
AT mannikkominna singlegeneticlocusassociatedwithpediatricfracturesagenomewideassociationstudyon3230patients
AT sinikumpujuhajaakko singlegeneticlocusassociatedwithpediatricfracturesagenomewideassociationstudyon3230patients