Common variations in BARD1 influence susceptibility to high-risk neuroblastoma.
We conducted a SNP-based genome-wide association study (GWAS) focused on the high-risk subset of neuroblastoma. As our previous unbiased GWAS showed strong association of common 6p22 SNP alleles with aggressive neuroblastoma, we restricted our analysis here to 397 high-risk cases compared to 2,043 controls. We detected new significant association of six SNPs at 2q35 within the BARD1 locus (P(allelic) = 2.35 x 10(-9)-2.25 x 10(-8)). We confirmed each SNP association in a second series of 189 high-risk cases and 1,178 controls (P(allelic) = 7.90 x 10(-7)-2.77 x 10(-4)). We also tested the two most significant SNPs (rs6435862, rs3768716) in two additional independent high-risk neuroblastoma case series, yielding combined allelic odds ratios of 1.68 each (P = 8.65 x 10(-18) and 2.74 x 10(-16), respectively). We also found significant association with known BARD1 nonsynonymous SNPs. These data show that common variation in BARD1 contributes to the etiology of the aggressive and most clinically relevant subset of human neuroblastoma.
Division of Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Mario
M
Capasso
Marcella
M
Devoto
Cuiping
C
Hou
Shahab
S
Asgharzadeh
Joseph T
JT
Glessner
Edward F
EF
Attiyeh
Yael P
YP
Mosse
Cecilia
C
Kim
Sharon J
SJ
Diskin
Kristina A
KA
Cole
Kristopher
K
Bosse
Maura
M
Diamond
Marci
M
Laudenslager
Cynthia
C
Winter
Jonathan P
JP
Bradfield
Richard H
RH
Scott
Jayanti
J
Jagannathan
Maria
M
Garris
Carmel
C
McConville
Wendy B
WB
London
Robert C
RC
Seeger
Struan F A
SF
Grant
Hongzhe
H
Li
Nazneen
N
Rahman
Eric
E
Rappaport
Hakon
H
Hakonarson
John M
JM
Maris
D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D009447:Neuroblastoma / Q000453:epidemiology / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
D025521:Tumor Suppressor Proteins; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases