title: Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility.
abstract: 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.
authors: Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. margaret.wrensch@ucsf.edu
authors: Margaret
authors: M
authors: Wrensch
authors: Robert B
authors: RB
authors: Jenkins
authors: Jeffrey S
authors: JS
authors: Chang
authors: Ru-Fang
authors: RF
authors: Yeh
authors: Yuanyuan
authors: Y
authors: Xiao
authors: Paul A
authors: PA
authors: Decker
authors: Karla V
authors: KV
authors: Ballman
authors: Mitchel
authors: M
authors: Berger
authors: Jan C
authors: JC
authors: Buckner
authors: Susan
authors: S
authors: Chang
authors: Caterina
authors: C
authors: Giannini
authors: Chandralekha
authors: C
authors: Halder
authors: Thomas M
authors: TM
authors: Kollmeyer
authors: Matthew L
authors: ML
authors: Kosel
authors: Daniel H
authors: DH
authors: LaChance
authors: Lucie
authors: L
authors: McCoy
authors: Brian P
authors: BP
authors: O'Neill
authors: Joe
authors: J
authors: Patoka
authors: Alexander R
authors: AR
authors: Pico
authors: Michael
authors: M
authors: Prados
authors: Charles
authors: C
authors: Quesenberry
authors: Terri
authors: T
authors: Rice
authors: Amanda L
authors: AL
authors: Rynearson
authors: Ivan
authors: I
authors: Smirnov
authors: Tarik
authors: T
authors: Tihan
authors: Joe
authors: J
authors: Wiemels
authors: Ping
authors: P
authors: Yang
authors: John K
authors: JK
authors: Wiencke
mesh_terms: 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
chemical_list: C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; C532890:RTEL1 protein, human; D004265:DNA Helicases