Lookup NU author(s): Professor Heather Cordell
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.In the past years, genome wide association studies (GWAS) have provided evidence that inter-individual susceptibility to diverse pathological conditions can reveal a common genetic architecture. Through the analysis of congenital heart disease (CHD) and neuroblastoma (NB) GWAS data, we aimed to dissect the genetic susceptibility shared between these conditions, which are known to arise from neural crest cell (NCC) migration or development abnormalities, via identification and functional characterization of common regions of association. Two loci (2q35 and 3q25.32) harbor single nucleotide polymorphisms (SNPs) that are associated at a p-value < 10−3 with conotruncal malformations and ventricular septal defect respectively, as well as with NB. In addition, the lead SNP in 4p16.2 for atrial septal defect and the lead SNP in 3q25.32 for tetralogy of Fallot are less than 250 Kb distant from the lead SNPs for NB at the same genomic regions. Some of these shared susceptibility loci regulate the expression of relevant genes involved in NCC formation and developmental processes (such as BARD1, MSX1, and SHOX2) and are enriched in several epigenetic markers from NB and fetal heart cell lines. Although the clinical correlation between NB and CHD is unclear, our exploration of a possible common genetic basis between NB and a subset of cardiac malformations can help shed light on their shared embryological origin and pathogenetic mechanisms.
Author(s): Testori A, Lasorsa VA, Cimmino F, Cantalupo S, Cardinale A, Avitabile M, Limongelli G, Russo MG, Diskin S, Maris J, Devoto M, Keavney B, Cordell HJ, Iolascon A, Capasso M
Publication type: Article
Publication status: Published
Online publication date: 30/08/2019
Acceptance date: 26/08/2019
Date deposited: 28/10/2019
ISSN (electronic): 2073-4425
Altmetrics provided by Altmetric