Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk

Kyle M. Walsh, Veryan Codd, Ivan V. Smirnov, Terri Rice, Paul A. Decker, Helen M. Hansen, Thomas Kollmeyer, Matthew L. Kosel, Annette M. Molinaro, Lucie S. McCoy, Paige M. Bracci, Belinda S. Cabriga, Melike Pekmezci, Shichun Zheng, Joseph L. Wiemels, Alexander R. Pico, Tarik Tihan, Mitchell S. Berger, Susan M. Chang, Michael D. PradosDaniel H Lachance, Brian Patrick O'Neill, Hugues Sicotte, Jeanette E Eckel-Passow, Pim Van Der Harst, John K. Wiencke, Nilesh J. Samani, Robert Brian Jenkins, Margaret R. Wrensch

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)731-735
Number of pages5
JournalNature Genetics
Volume46
Issue number7
DOIs
StatePublished - 2014

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Telomere
Glioma
Leukocytes
Alleles
Genome-Wide Association Study
Telomerase
telomerase RNA
Single Nucleotide Polymorphism
Meta-Analysis
Central Nervous System
Genome
Neoplasms

ASJC Scopus subject areas

  • Genetics

Cite this

Walsh, K. M., Codd, V., Smirnov, I. V., Rice, T., Decker, P. A., Hansen, H. M., ... Wrensch, M. R. (2014). Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk. Nature Genetics, 46(7), 731-735. https://doi.org/10.1038/ng.3004

Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk. / Walsh, Kyle M.; Codd, Veryan; Smirnov, Ivan V.; Rice, Terri; Decker, Paul A.; Hansen, Helen M.; Kollmeyer, Thomas; Kosel, Matthew L.; Molinaro, Annette M.; McCoy, Lucie S.; Bracci, Paige M.; Cabriga, Belinda S.; Pekmezci, Melike; Zheng, Shichun; Wiemels, Joseph L.; Pico, Alexander R.; Tihan, Tarik; Berger, Mitchell S.; Chang, Susan M.; Prados, Michael D.; Lachance, Daniel H; O'Neill, Brian Patrick; Sicotte, Hugues; Eckel-Passow, Jeanette E; Van Der Harst, Pim; Wiencke, John K.; Samani, Nilesh J.; Jenkins, Robert Brian; Wrensch, Margaret R.

In: Nature Genetics, Vol. 46, No. 7, 2014, p. 731-735.

Research output: Contribution to journalArticle

Walsh, KM, Codd, V, Smirnov, IV, Rice, T, Decker, PA, Hansen, HM, Kollmeyer, T, Kosel, ML, Molinaro, AM, McCoy, LS, Bracci, PM, Cabriga, BS, Pekmezci, M, Zheng, S, Wiemels, JL, Pico, AR, Tihan, T, Berger, MS, Chang, SM, Prados, MD, Lachance, DH, O'Neill, BP, Sicotte, H, Eckel-Passow, JE, Van Der Harst, P, Wiencke, JK, Samani, NJ, Jenkins, RB & Wrensch, MR 2014, 'Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk', Nature Genetics, vol. 46, no. 7, pp. 731-735. https://doi.org/10.1038/ng.3004
Walsh, Kyle M. ; Codd, Veryan ; Smirnov, Ivan V. ; Rice, Terri ; Decker, Paul A. ; Hansen, Helen M. ; Kollmeyer, Thomas ; Kosel, Matthew L. ; Molinaro, Annette M. ; McCoy, Lucie S. ; Bracci, Paige M. ; Cabriga, Belinda S. ; Pekmezci, Melike ; Zheng, Shichun ; Wiemels, Joseph L. ; Pico, Alexander R. ; Tihan, Tarik ; Berger, Mitchell S. ; Chang, Susan M. ; Prados, Michael D. ; Lachance, Daniel H ; O'Neill, Brian Patrick ; Sicotte, Hugues ; Eckel-Passow, Jeanette E ; Van Der Harst, Pim ; Wiencke, John K. ; Samani, Nilesh J. ; Jenkins, Robert Brian ; Wrensch, Margaret R. / Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk. In: Nature Genetics. 2014 ; Vol. 46, No. 7. pp. 731-735.
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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.",
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T1 - Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk

AU - Walsh, Kyle M.

AU - Codd, Veryan

AU - Smirnov, Ivan V.

AU - Rice, Terri

AU - Decker, Paul A.

AU - Hansen, Helen M.

AU - Kollmeyer, Thomas

AU - Kosel, Matthew L.

AU - Molinaro, Annette M.

AU - McCoy, Lucie S.

AU - Bracci, Paige M.

AU - Cabriga, Belinda S.

AU - Pekmezci, Melike

AU - Zheng, Shichun

AU - Wiemels, Joseph L.

AU - Pico, Alexander R.

AU - Tihan, Tarik

AU - Berger, Mitchell S.

AU - Chang, Susan M.

AU - Prados, Michael D.

AU - Lachance, Daniel H

AU - O'Neill, Brian Patrick

AU - Sicotte, Hugues

AU - Eckel-Passow, Jeanette E

AU - Van Der Harst, Pim

AU - Wiencke, John K.

AU - Samani, Nilesh J.

AU - Jenkins, Robert Brian

AU - Wrensch, Margaret R.

PY - 2014

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N2 - 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.

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