Phenotype restricted genome-wide association study using a gene-centric approach identifies three low-risk neuroblastoma susceptibility Loci.

• Main Authors: Le B Nguyen, 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, John M Maris
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2011-03-01
• Series: PLoS Genetics
• Online Access: http://europepmc.org/articles/PMC3060064?pdf=render
• ISSN: 1553-7390; 1553-7404

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.