title: Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk.
abstract: Glioma, the most common central nervous system cancer in adults, has poor prognosis. Here we identify a new SNP associated with glioma risk, rs1920116 (near TERC), that reached genome-wide significance (Pcombined = 8.3 × 10(-9)) in a meta-analysis of genome-wide association studies (GWAS) of high-grade glioma and replication data (1,644 cases and 7,736 controls). This region has previously been associated with mean leukocyte telomere length (LTL). We therefore examined the relationship between LTL and both this new risk locus and other previously established risk loci for glioma using data from a recent GWAS of LTL (n = 37,684 individuals). Alleles associated with glioma risk near TERC and TERT were strongly associated with longer LTL (P = 5.5 × 10(-20) and 4.4 × 10(-19), respectively). In contrast, risk-associated alleles near RTEL1 were inconsistently associated with LTL, suggesting the presence of distinct causal alleles. No other risk loci for glioma were associated with LTL. The identification of risk alleles for glioma near TERC and TERT that also associate with telomere length implicates telomerase in gliomagenesis.
authors.affiliation: 1] Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. [2] Program in Cancer Genetics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Walsh
authors.affiliation: 1] Department of Cardiovascular Sciences, University of Leicester, Leicester, UK. [2] National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
authors.forename: Veryan
authors.initials: V
authors.lastname: Codd
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Ivan V
authors.initials: IV
authors.lastname: Smirnov
authors.affiliation: Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Terri
authors.initials: T
authors.lastname: Rice
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Decker
authors.affiliation: Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Hansen
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kollmeyer
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Kosel
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Annette M
authors.initials: AM
authors.lastname: Molinaro
authors.affiliation: Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Lucie S
authors.initials: LS
authors.lastname: McCoy
authors.affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Paige M
authors.initials: PM
authors.lastname: Bracci
authors.affiliation: Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Belinda S
authors.initials: BS
authors.lastname: Cabriga
authors.affiliation: Department of Pathology, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Melike
authors.initials: M
authors.lastname: Pekmezci
authors.affiliation: Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Shichun
authors.initials: S
authors.lastname: Zheng
authors.affiliation: 1] Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. [2] Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA. [3] Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Wiemels
authors.affiliation: 1] Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. [2] Department of Bioinformatics, Gladstone Institutes, San Francisco, California, USA.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Pico
authors.affiliation: Department of Pathology, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Tarik
authors.initials: T
authors.lastname: Tihan
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Berger
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Chang
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Prados
authors.affiliation: Department of Neurology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Lachance
authors.affiliation: Department of Neurology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors.forename: Brian Patrick
authors.initials: BP
authors.lastname: O'Neill
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors.forename: Hugues
authors.initials: H
authors.lastname: Sicotte
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors.forename: Jeanette E
authors.initials: JE
authors.lastname: Eckel-Passow
authors.affiliation: 1] Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. [2] Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Pim
authors.initials: P
authors.lastname: van der Harst
authors.affiliation: 1] Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. [2] Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA.
authors.forename: John K
authors.initials: JK
authors.lastname: Wiencke
authors.affiliation: 1] Department of Cardiovascular Sciences, University of Leicester, Leicester, UK. [2] National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
authors.forename: Nilesh J
authors.initials: NJ
authors.lastname: Samani
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jenkins
authors.affiliation: 1] Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. [2] Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Wrensch
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D055106:Genome-Wide Association Study; D005838:Genotype; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology; D060787:Neoplasm Grading; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012313:RNA / Q000235:genetics*; D012307:Risk Factors; D019098:Telomerase / Q000235:genetics*; D016615:Telomere / Q000235:genetics*
chemical_list: C422952:telomerase RNA; D012313:RNA; C509186:TERT protein, human; D019098:Telomerase