Table 1.

Summary of genomic loci significantly associated with neuroblastoma predisposition.

Genomic Locus	Candidate Gene	Phenotype association	Top SNP	P-Value (combined)	MAF cases	Odds Ratio (OR)	Proposed Mechanism	Level of Evidence#
6p22	CASC15/NBAT-1	High-risk	rs6939340	9.33 × 10−15	56%	1.37	Loss of function	223, 31, 33
2q35	BARD1	High-risk	rs6435862	8.65 × 10−18	40%	1.68	Gain of function	221, 32
11p15	LMO1	High-risk	rs110419	5.20 ×10−16	55%	1.34	Gain of function	120, 34
6q16	LIN28B	High-risk	rs17065417	1.2 × 10−8	8%	1.38	Gain of function	119, 51
6q16	HACE1	High-risk	rs4336470	2.7 × 10−7	30%	1.26	Loss of function	319
1q23	DUSP12	Low-risk	rs1027702	2.07 × 10−6	31%	2.01	unknown	429
5q11	DDX4	Low-risk	rs2619046	2.94 ×10−6	32%	1.47	unknown	429
5q11	IL31RA	Low-risk	rs10055201	6.54 × 10−7	29%	1.49	unknown	429
11p11	HSD17B12	Low-risk	rs11037575	4.20 × 10−7	39%	1.67	unknown	429
8p21	NEFL	-	rs11994014	0.005	20%	0.88	Loss of function	225
17p13	TP53	-	rs35850753	3.43 × 10−14	3.6%	2.70	Loss of function	126, 52
1q21	NBPF23	-	CNV	2.97 × 10−17	15%	2.49	unknown	430

^#Level of evidence 1 = strong functional/mechanistic evidence of being a neuroblastoma associated gene, 2 = some functional/mechanistic evidence in neuroblastoma, 3 = some functional/mechanistic evidence in other malignancies, 4 = biological function in neuroblastoma/other malignancies unknown. MAF = minor allele frequency.

Multiple genomic loci are associated with a specific neuroblastoma clinical phenotype as detailed and have strong functional evidence linking the associated genes to neuroblastoma genesis, while others have functions that have yet to be explored in neuroblastoma (right). P values and ORs are based on combined results from discovery and replication cohorts from the original publication as indicated.