Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility.
The causes of glioblastoma and other gliomas remain obscure. To discover new candidate genes influencing glioma susceptibility, we conducted a principal component-adjusted genome-wide association study (GWAS) of 275,895 autosomal variants among 692 adult high-grade glioma cases (622 from the San Francisco Adult Glioma Study (AGS) and 70 from the Cancer Genome Atlas (TCGA)) and 3,992 controls (602 from AGS and 3,390 from Illumina iControlDB (iControls)). For replication, we analyzed the 13 SNPs with P < 10(-6) using independent data from 176 high-grade glioma cases and 174 controls from the Mayo Clinic. On 9p21, rs1412829 near CDKN2B had discovery P = 3.4 x 10(-8), replication P = 0.0038 and combined P = 1.85 x 10(-10). On 20q13.3, rs6010620 intronic to RTEL1 had discovery P = 1.5 x 10(-7), replication P = 0.00035 and combined P = 3.40 x 10(-9). For both SNPs, the direction of association was the same in discovery and replication phases.
Wrensch
Margaret
M
Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. margaret.wrensch@ucsf.edu
Jenkins
Robert B
RB
Chang
Jeffrey S
JS
Yeh
Ru-Fang
RF
Xiao
Yuanyuan
Y
Decker
Paul A
PA
Ballman
Karla V
KV
Berger
Mitchel
M
Buckner
Jan C
JC
Chang
Susan
S
Giannini
Caterina
C
Halder
Chandralekha
C
Kollmeyer
Thomas M
TM
Kosel
Matthew L
ML
LaChance
Daniel H
DH
McCoy
Lucie
L
O'Neill
Brian P
BP
Patoka
Joe
J
Pico
Alexander R
AR
Prados
Michael
M
Quesenberry
Charles
C
Rice
Terri
T
Rynearson
Amanda L
AL
Smirnov
Ivan
I
Tihan
Tarik
T
Wiemels
Joe
J
Yang
Ping
P
Wiencke
John K
JK
D000328:Adult; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D015894:Genome, Human / Q000235:genetics; D055106:Genome-Wide Association Study; D005910:Glioma / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D025341:Principal Component Analysis; D012044:Regression Analysis
C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; C532890:RTEL1 protein, human; D004265:DNA Helicases