Phenotype Restricted Genome-Wide Association Study Using a Gene-Centric Approach Identifies Three Low-Risk Neuroblastoma Susceptibility Loci

Lễ B Nguyễn, Sharon J Diskin, Mario Capasso, Kai Wang, Maura A Diamond, Joseph Glessner, Cecilia Kim, Edward F Attiyeh, Yael P Mosse, Kristina Cole, Achille Iolascon, Marcella Devoto, Hakon Hakonarson, Hongzhe K Li and John M Maris

PLOS Genetics, 2011, vol. 7, issue 3, 1-9

Abstract: Neuroblastoma is a malignant neoplasm of the developing sympathetic nervous system that is notable for its phenotypic diversity. High-risk patients typically have widely disseminated disease at diagnosis and a poor survival probability, but low-risk patients frequently have localized tumors that are almost always cured with little or no chemotherapy. Our genome-wide association study (GWAS) has identified common variants within FLJ22536, BARD1, and LMO1 as significantly associated with neuroblastoma and more robustly associated with high-risk disease. Here we show that a GWAS focused on low-risk cases identified SNPs within DUSP12 at 1q23.3 (P = 2.07×10−6), DDX4 and IL31RA both at 5q11.2 (P = 2.94×10−6 and 6.54×10−7 respectively), and HSD17B12 at 11p11.2 (P = 4.20×10−7) as being associated with the less aggressive form of the disease. These data demonstrate the importance of robust phenotypic data in GWAS analyses and identify additional susceptibility variants for neuroblastoma. Author Summary: Neuroblastoma is the most common solid tumor outside the central nervous system and is accountable for 10% of the mortality rate of all children's cancers. It has distinctive clinical behaviors and is categorized into different risk groups: high-risk, intermediate-risk, and low-risk. Genome-wide association studies have reported a number of genetic variations predisposing to high-risk neuroblastoma. This study focuses on the low-risk neuroblastoma group and identifies four novel genes (DUSP12, DDX4, IL31RA, and HSD17B12) at three distinct genomic positions that harbor disease-causing variants. This study also reports several gene sets that are enriched in overall neuroblastoma as well as in both high-risk and low-risk groups. Also of importance is that this study adopts a new computational method that identifies genes, instead of only one single nucleotide polymorphism, as disease-causing variants. Shown to have superior power of detection genome-wide association signals for neuroblastoma, the methodology presented in this study has great potential applications in case-control association studies in other diseases.

Date: 2011
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1002026 (text/html)
https://journals.plos.org/plosgenetics/article/fil ... 02026&type=printable (application/pdf)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:plo:pgen00:1002026

DOI: 10.1371/journal.pgen.1002026

Access Statistics for this article

More articles in PLOS Genetics from Public Library of Science
Bibliographic data for series maintained by plosgenetics ().