title: A low-frequency variant at 8q24.21 is strongly associated with risk of oligodendroglial tumors and astrocytomas with IDH1 or IDH2 mutation.
abstract: Variants at 8q24.21 have been shown to be associated with glioma development. By means of tag SNP genotyping and imputation, pooled next-generation sequencing using long-range PCR and subsequent validation SNP genotyping, we identified seven low-frequency SNPs at 8q24.21 that were strongly associated with glioma risk (P=1×10(-25) to 1×10(-14)). The most strongly associated SNP, rs55705857, remained highly significant after individual adjustment for the other top six SNPs and two previously published SNPs. After stratifying by histological and tumor genetic subtype, the most significant associations of rs55705857 were with oligodendroglial tumors and gliomas with mutant IDH1 or IDH2 (odds ratio (OR)=5.1, P=1.1×10(-31) and OR=4.8, P=6.6×10(-22), respectively). Strong associations were observed for astrocytomas with mutated IDH1 or IDH2 (grades 2-4) (OR=5.16-6.66, P=4.7×10(-12) to 2.2×10(-8)) but not for astrocytomas with wild-type IDH1 and IDH2 (smallest P=0.26). The conserved sequence block that includes rs55705857 is consistently modeled as a microRNA.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. rjenkins@mayo.edu
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jenkins
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Xiao
authors.forename: Hugues
authors.initials: H
authors.lastname: Sicotte
authors.forename: Paul A
authors.initials: PA
authors.lastname: Decker
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Kollmeyer
authors.forename: Helen M
authors.initials: HM
authors.lastname: Hansen
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Kosel
authors.forename: Shichun
authors.initials: S
authors.lastname: Zheng
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Walsh
authors.forename: Terri
authors.initials: T
authors.lastname: Rice
authors.forename: Paige
authors.initials: P
authors.lastname: Bracci
authors.forename: Lucie S
authors.initials: LS
authors.lastname: McCoy
authors.forename: Ivan
authors.initials: I
authors.lastname: Smirnov
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Patoka
authors.forename: George
authors.initials: G
authors.lastname: Hsuang
authors.forename: Joe L
authors.initials: JL
authors.lastname: Wiemels
authors.forename: Tarik
authors.initials: T
authors.lastname: Tihan
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Pico
authors.forename: Michael D
authors.initials: MD
authors.lastname: Prados
authors.forename: Susan M
authors.initials: SM
authors.lastname: Chang
authors.forename: Mitchel S
authors.initials: MS
authors.lastname: Berger
authors.forename: Alissa A
authors.initials: AA
authors.lastname: Caron
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Fink
authors.forename: Chandralekha
authors.initials: C
authors.lastname: Halder
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Rynearson
authors.forename: Brooke L
authors.initials: BL
authors.lastname: Fridley
authors.forename: Jan C
authors.initials: JC
authors.lastname: Buckner
authors.forename: Brian P
authors.initials: BP
authors.lastname: O'Neill
authors.forename: Caterina
authors.initials: C
authors.lastname: Giannini
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Lachance
authors.forename: John K
authors.initials: JK
authors.lastname: Wiencke
authors.forename: Jeanette E
authors.initials: JE
authors.lastname: Eckel-Passow
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Wrensch
mesh_terms: D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D002898:Chromosomes, Human, Pair 8; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009837:Oligodendroglioma / Q000201:enzymology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D062085:RNA, Long Noncoding; D012307:Risk Factors; D017422:Sequence Analysis, DNA
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D062085:RNA, Long Noncoding; C000613877:long noncoding RNA CCDC26, human; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human