Cancer Res Treat.  2020 Oct;52(4):1251-1261. 10.4143/crt.2020.140.

Genome-Wide Association Study for the Identification of Novel Genetic Variants Associated with the Risk of Neuroblastoma in Korean Children

• Bae JS
• Lee JW
• Yoo JE
• Joung JG
• Yoo KH
• Koo HH
• Song YM
• Sung KW

• KMID: 2507950
• DOI: http://doi.org/10.4143/crt.2020.140

Abstract

Purpose
Neuroblastoma (NB) is the most common extracranial solid tumor found in children. To identify significant genetic factors for the risk of NB, several genetic studies was conducted mainly for Caucasians and Europeans. However, considering racial differences, there is a possibility that genetic predispositions that contribute to the development of NB are different, and GWAS study has not yet been conducted on Korean NB patients.
Materials and Methods
To identify the genetic variations associated with the risk of pediatric NB in Korean children, we performed a genome-wide association analysis with 296 NB patients and 1000 unaffected controls (total n = 1,296) after data cleaning and filtering as well as imputation of non-genotyped SNPs using IMPUTE v2.3.2.
Results
After adjusting for multiple comparisons, we found 21 statistically significant SNPs associated with the risk of NB (P^corr < 0.05) within 12 genes (RPTN, MRPS18B, LRRC45, KANSL1L, ARHGEF40, IL15RA, L1TD1, ANO7, LAMA5, OR7G2, SALL4, and NEUROG2). Interestingly, out of these, 12 markers were nonsynonymous SNPs. The SNP rs76015112 was most significantly associated with the risk of NB (p = 8.1E-23, P^corr = 2.3E-17) and was located in the RPTN gene. In addition, significant nonsynonymous SNPs in ADGRE1 were found in patients with MYCN amplification (rs7256147, p = 2.6E-05). In high-risk group, rs7256147 was observed as a significant SNP (p = 5.9E-06).
Conclusion
Our findings might facilitate improved understanding of the mechanism of pediatric NB pathogenesis. However, functional evaluation and replication of these results in other populations are still needed.

Keyword

Neuroblastoma; Genetic variation; Genome wide association study; amplification; high risk; Korean children

Figure

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  Fig. 1. (A) The p-values of genome-wide association study. The Manhattan plot shows the p-values for the risk of neuroblastoma using logistic regression analysis. x-axis represents the single nucleotide polymorphism (SNP) markers on each chromosome. The highest p-value (p=8.1E-23, pcorr=2.3E-17) was observed in rs76015112 on 1q21.3. (B) Regional association plots at the RPTN. Regional association plots including both genotyped and SNPs for the RPTN was generated by LocusZoom within 400 kb. The significance of association (−log10-transformed p-values) and the recombination rate are plotted. SNPs are colored to reflect pairwise linkage disequilibrium (r2) with the most significantly associated genotyped SNP in the 1000 Genomes Project Phase 1 interim release Asian (ASN) population genotypes. The most significant genotyped SNPs are labeled and shown in purple.

Reference

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