Table 2.

Germline neuroblastoma-associated variants identified by GWAS.

Genomic Location	Variant	Candidate Gene(s)	Combined P-value	Odds Ratio (Confidence Interval)	Reference/ Alternate Allelea	MAFb in European Cases/ Controls	Clinical or Biological Subset	Populations Studiedc					Proposed Mechanism	References for Association
								EA	UK	IT	AA	SC
Single Nucleotide Polymorphisms (most significant SNP from the original study is shown)
6p22	rs6939340	CASC15 and NBAT-1	9.3×10−15	1.37 (1.27–1.49)	A/G	0.56/0.47	High-risk	✓	✓	✓	✓g	✓	Decreased expression (Russell et al. 2015; Pandey et al. 2014)	Maris et al. 2008; Latorre et al. 2012; Capasso et al. 2013; He, Zhang et al. 2016
2q35	rs6435862	BARD1	8.7×10−18	1.68 (1.49–1.90)	T/G	0.40/0.29	High-risk	✓	✓	✓	✓	✓	Expression of oncogenic isoform (Bosse et al. 2012)	Capasso et al. 2009, Latorre et al. 2012; Capasso et al. 2013; Zhang et al. 2016
11p15.4	rs2168101d	LMO1	7.5×10−29	0.65 (0.60-0.70)	G/T	0.24/0.31	High-risk	✓	✓	✓	✓g	✓h	Increased expression (Oldridge et al. 2015)	Wang et al. 2011; Oldridge et al. 2015; He, Zhong et al. 2016
1q23.3	rs1027702	DUSP12e	2.1×10−6	2.01 (1.47-2.79)	C/T	Not reported	Low-risk	✓		✓			Unknown	Nguyen et al. 2011
11p11.2	rs11037575	HSD17B12e	4.2×10−7	1.67 (1.35-2.08)	C/T	Not reported	Low-risk	✓		✓		✓	Unknown	Nguyen et al. 2011; Zhang, Zou et al. 2017
5q11.2	rs2619046	DDX4e	2.9×10−6	1.48 (1.21-1.79)	C/T	Not reported	Low-risk	✓		✓			Unknown	Nguyen et al. 2011
5q11.2	rs10055201	IL31RAe	6.5×10−7	1.49 (1.23-1.81)	A/G	Not reported	Low-risk	✓					Unknown	Nguyen et al. 2011
2q34	rs1033069	SPAG16f	6.4×10−5	Not reported	G/A	Not reported	High-risk	✓			✓		Unknown	Gamazon et al. 2013
6q16	rs4336470	HACE1	2.7×10−11	1.26 (1.18-1.35)	C/T	0.30/0.35	None	✓		✓	✓	✓i	Decreased expression (Diskin et al. 2012)	Diskin et al. 2012; Zhang, Zhang et al. 2017
6q16	rs17065417	LIN28B	1.2×10−8	1.38 (1.23-1.54)	A/C	0.08/0.11	None	✓		✓	✓	✓h	Increased expression (Diskin et al. 2012)	Diskin et al. 2012; He, Yang et al. 2016
17p13.1	rs35850753	TP53	3.4×10−12	2.7 (2.0-3.6)	T/C	0.04/0.02	None	✓		✓	✓		rs35850753: increased expression of dominant-negative variant (Fujita et al. 2009); rs78378222: impaired polyadenylation (Stacey et al. 2011, Diskin et al. 2014)	Diskin et al. 2014
8p21	rs1059111	NEFL	4.9×10−3	0.86 (0.77-0.95)	T/A	0.12/0.13	None	✓		✓			Increased expression (Capasso et al. 2014)	Capasso et al. 2014
3q25	rs6441201	MLF1 and RSRC1	1.2×10−11	1.23 (1.16-1.31)	G/A	0.52/0.47	None	✓	✓	✓	✓		Increased expression of MLF1 (Lee et al. 2017)	Lee et al. 2017
4p16	rs3796727	CPZ	1.3×10−12	1.30 (1.21-1.40)	G/A	0.35/0.30	None	✓	✓	✓			Decreased methylation (Lee et al. 2017)	Lee et al. 2017
12p13	rs34330	CDKN1B	0.002	1.15 (1.06-1.24)	C/T	0.26/0.23	None	✓		✓			Increased expression (Capasso et al. 2017)	Capasso et al. 2017
11q22.2	rs10895322	MMP20	2.6×10−9	2.89 (1.99-4.10)	A/G	0.16/0.06	11q deletion	✓					Increased expression (Chang et al. 2017)	Chang et al. 2017
3p21.31	rs80059929	KIF15	6.5×10−12	2.95 (2.17-4.02)	T/A	0.09/0.04	MYCN amplification	✓					Unknown	Hungate et al. 2017
Copy Number Variations
1q21.1	hg18: 147,292,384–147,435,422	NBPF23	3.0×10−17	2.49 (2.02-3.05)	143-kb deletion	0.16/0.09	None	✓					Unknown	Diskin et al. 2009

^aRisk allele is displayed in bold.

^bMAF=Minor Allele Frequency.

^cAssociation replicated unless otherwise noted. EA = European American, UK = United Kingdom, IT = Italian, AA = African American, SC = Southern Chinese.

^dThis was not the top SNP in the original study, but was demonstrated as the causal SNP in Oldridge et al. 2015.

^eGene-based study: p-values were calculated at the gene level rather than the SNP level, and allele frequencies were not provided.

^fCase-only study (association with high-risk neuroblastoma was tested): odds ratio and control MAF were not reported.

^gThis association did not replicate.

^hA different SNP at the same locus was analyzed.

ⁱAssociation represents a combined analysis of five SNPs.