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

被引:154
作者
Walsh, Kyle M. [1 ,2 ]
Codd, Veryan [3 ,4 ]
Smirnov, Ivan V. [5 ]
Rice, Terri [1 ]
Decker, Paul A. [6 ]
Hansen, Helen M. [1 ]
Kollmeyer, Thomas [7 ]
Kosel, Matthew L. [6 ]
Molinaro, Annette M. [5 ]
McCoy, Lucie S. [1 ]
Bracci, Paige M. [8 ]
Cabriga, Belinda S. [1 ]
Pekmezci, Melike [9 ]
Zheng, Shichun [1 ]
Wiemels, Joseph L. [1 ,8 ,10 ]
Pico, Alexander R. [1 ,11 ]
Tihan, Tarik [9 ]
Berger, Mitchell S. [5 ]
Chang, Susan M. [5 ]
Prados, Michael D. [5 ]
Lachance, Daniel H. [12 ]
O'Neill, Brain Patrick [12 ]
Sicotte, Hugues [6 ]
Eckel-Passow, Jeanette E. [6 ]
van der Harst, Pim [13 ,14 ]
Wiencke, John K. [1 ,10 ]
Samani, Nilesh J. [3 ,4 ]
Jenkins, Robert B. [7 ]
Wrensch, Margaret R. [1 ,10 ]
机构
[1] Univ Calif San Francisco, Dept Neurol Surg, Div Neuroepidemiol, San Francisco, CA 94132 USA
[2] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Program Canc Genet, San Francisco, CA USA
[3] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England
[4] Glenfield Hosp, Nat Inst Hlth Res, Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England
[5] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA
[6] Mayo Clin, Coll Med, Div Biomed Stat & Informat, Rochester, MN USA
[7] Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN USA
[8] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA
[9] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA
[10] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA USA
[11] Gladstone Inst, Dept Bioinformat, San Francisco, CA USA
[12] Mayo Clin, Coll Med, Dept Neurol, Rochester, MN USA
[13] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands
[14] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands
基金
美国国家卫生研究院;
关键词
GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; PROMOTER MUTATIONS; CARDIOVASCULAR-DISEASE; COLORECTAL-CANCER; GLIOBLASTOMA; METAANALYSIS; PATHWAYS; MELANOMA; HUMANS;
D O I
10.1038/ng.3004
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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 (P-combined = 8.3 x 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)(1). Alleles associated with glioma risk near TERC and TERT were strongly associated with longer LTL (P = 5.5 x 10(-20) and 4.4 x 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.
引用
收藏
页码:731 / 735
页数:5
相关论文
共 33 条
  • [1] Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer
    Bojesen, Stig E.
    Pooley, Karen A.
    Johnatty, Sharon E.
    Beesley, Jonathan
    Michailidou, Kyriaki
    Tyrer, Jonathan P.
    Edwards, Stacey L.
    Pickett, Hilda A.
    Shen, Howard C.
    Smart, Chanel E.
    Hillman, Kristine M.
    Mai, Phuong L.
    Lawrenson, Kate
    Stutz, Michael D.
    Lu, Yi
    Karevan, Rod
    Woods, Nicholas
    Johnston, Rebecca L.
    French, Juliet D.
    Chen, Xiaoqing
    Weischer, Maren
    Nielsen, Sune F.
    Maranian, Melanie J.
    Ghoussaini, Maya
    Ahmed, Shahana
    Baynes, Caroline
    Bolla, Manjeet K.
    Wang, Qin
    Dennis, Joe
    McGuffog, Lesley
    Barrowdale, Daniel
    Lee, Andrew
    Healey, Sue
    Lush, Michael
    Tessier, Daniel C.
    Vincent, Daniel
    Bacot, Francis
    Vergote, Ignace
    Lambrechts, Sandrina
    Despierre, Evelyn
    Risch, Harvey A.
    Gonzalez-Neira, Anna
    Rossing, Mary Anne
    Pita, Guillermo
    Doherty, Jennifer A.
    Alvarez, Nuria
    Larson, Melissa C.
    Fridley, Brooke L.
    Schoof, Nils
    Chang-Claude, Jenny
    [J]. NATURE GENETICS, 2013, 45 (04) : 371 - 384
  • [2] Telomere length, risk of coronary heart disease, and statin treatment in the West of Scotland Primary Prevention Study: a nested case-control study
    Brouilette, Scott W.
    Moore, Jasbir S.
    D McMahon, Alex
    Thompson, John R.
    Ford, Ian
    Shepherd, James
    Packard, Chris J.
    Samani, Nilesh J.
    [J]. LANCET, 2007, 369 (9556) : 107 - 114
  • [3] Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
    Burton, Paul R.
    Clayton, David G.
    Cardon, Lon R.
    Craddock, Nick
    Deloukas, Panos
    Duncanson, Audrey
    Kwiatkowski, Dominic P.
    McCarthy, Mark I.
    Ouwehand, Willem H.
    Samani, Nilesh J.
    Todd, John A.
    Donnelly, Peter
    Barrett, Jeffrey C.
    Davison, Dan
    Easton, Doug
    Evans, David
    Leung, Hin-Tak
    Marchini, Jonathan L.
    Morris, Andrew P.
    Spencer, Chris C. A.
    Tobin, Martin D.
    Attwood, Antony P.
    Boorman, James P.
    Cant, Barbara
    Everson, Ursula
    Hussey, Judith M.
    Jolley, Jennifer D.
    Knight, Alexandra S.
    Koch, Kerstin
    Meech, Elizabeth
    Nutland, Sarah
    Prowse, Christopher V.
    Stevens, Helen E.
    Taylor, Niall C.
    Walters, Graham R.
    Walker, Neil M.
    Watkins, Nicholas A.
    Winzer, Thilo
    Jones, Richard W.
    McArdle, Wendy L.
    Ring, Susan M.
    Strachan, David P.
    Pembrey, Marcus
    Breen, Gerome
    St Clair, David
    Caesar, Sian
    Gordon-Smith, Katherine
    Jones, Lisa
    Fraser, Christine
    Green, Elain K.
    [J]. NATURE, 2007, 447 (7145) : 661 - 678
  • [4] Telomere-based crisis: functional differences between telomerase activation and ALT in tumor progression
    Chang, S
    Khoo, CM
    Naylor, ML
    Maser, RS
    DePinho, RA
    [J]. GENES & DEVELOPMENT, 2003, 17 (01) : 88 - 100
  • [5] Comprehensive genomic characterization defines human glioblastoma genes and core pathways
    Chin, L.
    Meyerson, M.
    Aldape, K.
    Bigner, D.
    Mikkelsen, T.
    VandenBerg, S.
    Kahn, A.
    Penny, R.
    Ferguson, M. L.
    Gerhard, D. S.
    Getz, G.
    Brennan, C.
    Taylor, B. S.
    Winckler, W.
    Park, P.
    Ladanyi, M.
    Hoadley, K. A.
    Verhaak, R. G. W.
    Hayes, D. N.
    Spellman, Paul T.
    Absher, D.
    Weir, B. A.
    Ding, L.
    Wheeler, D.
    Lawrence, M. S.
    Cibulskis, K.
    Mardis, E.
    Zhang, Jinghui
    Wilson, R. K.
    Donehower, L.
    Wheeler, D. A.
    Purdom, E.
    Wallis, J.
    Laird, P. W.
    Herman, J. G.
    Schuebel, K. E.
    Weisenberger, D. J.
    Baylin, S. B.
    Schultz, N.
    Yao, Jun
    Wiedemeyer, R.
    Weinstein, J.
    Sander, C.
    Gibbs, R. A.
    Gray, J.
    Kucherlapati, R.
    Lander, E. S.
    Myers, R. M.
    Perou, C. M.
    McLendon, Roger
    [J]. NATURE, 2008, 455 (7216) : 1061 - 1068
  • [6] Identification of seven loci affecting mean telomere length and their association with disease
    Codd, Veryan
    Nelson, Christopher P.
    Albrecht, Eva
    Mangino, Massimo
    Deelen, Joris
    Buxton, Jessica L.
    Hottenga, Jouke Jan
    Fischer, Krista
    Esko, Tonu
    Surakka, Ida
    Broer, Linda
    Nyholt, Dale R.
    Leach, Irene Mateo
    Salo, Perttu
    Hagg, Sara
    Matthews, Mary K.
    Palmen, Jutta
    Norata, Giuseppe D.
    O'Reilly, Paul F.
    Saleheen, Danish
    Amin, Najaf
    Balmforth, Anthony J.
    Beekman, Marian
    de Boer, Rudolf A.
    Bohringer, Stefan
    Braund, Peter S.
    Burton, Paul R.
    de Craen, Anton J. M.
    Denniff, Matthew
    Dong, Yanbin
    Douroudis, Konstantinos
    Dubinina, Elena
    Eriksson, Johan G.
    Garlaschelli, Katia
    Guo, Dehuang
    Hartikainen, Anna-Liisa
    Henders, Anjali K.
    Houwing-Duistermaat, Jeanine J.
    Kananen, Laura
    Karssen, Lennart C.
    Kettunen, Johannes
    Klopp, Norman
    Lagou, Vasiliki
    van Leeuwen, Elisabeth M.
    Madden, Pamela A.
    Maegi, Reedik
    Magnusson, Patrik K. E.
    Mannisto, Satu
    McCarthy, Mark I.
    Medland, Sarah E.
    [J]. NATURE GENETICS, 2013, 45 (04) : 422 - 427
  • [7] Common variants near TERC are associated with mean telomere length
    Codd, Veryan
    Mangino, Massimo
    van der Harst, Pim
    Braund, Peter S.
    Kaiser, Michael
    Beveridge, Alan J.
    Rafelt, Suzanne
    Moore, Jasbir
    Nelson, Chris
    Soranzo, Nicole
    Zhai, Guangju
    Valdes, Ana M.
    Blackburn, Hannah
    Leach, Irene Mateo
    de Boer, Rudolf A.
    Goodall, Alison H.
    Ouwehand, Willem
    van Veldhuisen, Dirk J.
    van Gilst, Wiek H.
    Navis, Gerjan
    Burton, Paul R.
    Tobin, Martin D.
    Hall, Alistair S.
    Thompson, John R.
    Spector, Tim
    Samani, Nilesh J.
    [J]. NATURE GENETICS, 2010, 42 (03) : 197 - 199
  • [8] Longer Leukocyte Telomeres Are Associated with Ultra-Endurance Exercise Independent of Cardiovascular Risk Factors
    Denham, Joshua
    Nelson, Christopher P.
    O'Brien, Brendan J.
    Nankervis, Scott A.
    Denniff, Matthew
    Harvey, Jack T.
    Marques, Francine Z.
    Codd, Veryan
    Zukowska-Szczechowska, Ewa
    Samani, Nilesh J.
    Tomaszewski, Maciej
    Charchar, Fadi J.
    [J]. PLOS ONE, 2013, 8 (07):
  • [9] Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis
    Fingerlin, Tasha E.
    Murphy, Elissa
    Zhang, Weiming
    Peljto, Anna L.
    Brown, Kevin K.
    Steele, Mark P.
    Loyd, James E.
    Cosgrove, Gregory P.
    Lynch, David
    Groshong, Steve
    Collard, Harold R.
    Wolters, Paul J.
    Bradford, Williamson Z.
    Kossen, Karl
    Seiwert, Scott D.
    du Bois, Roland M.
    Garcia, Christine Kim
    Devine, Megan S.
    Gudmundsson, Gunnar
    Isaksson, Helgi J.
    Kaminski, Naftali
    Zhang, Yingze
    Gibson, Kevin F.
    Lancaster, Lisa H.
    Cogan, Joy D.
    Mason, Wendi R.
    Maher, Toby M.
    Molyneaux, Philip L.
    Wells, Athol U.
    Moffatt, Miriam F.
    Selman, Moises
    Pardo, Annie
    Kim, Dong Soon
    Crapo, James D.
    Make, Barry J.
    Regan, Elizabeth A.
    Walek, Dinesha S.
    Daniel, Jerry J.
    Kamatani, Yoichiro
    Zelenika, Diana
    Smith, Keith
    McKean, David
    Pedersen, Brent S.
    Talbert, Janet
    Kidd, Raven N.
    Markin, Cheryl R.
    Beckman, Kenneth B.
    Lathrop, Mark
    Schwarz, Marvin I.
    Schwartz, David A.
    [J]. NATURE GENETICS, 2013, 45 (06) : 613 - +
  • [10] Fitzpatrick AL, 2007, AM J EPIDEMIOL, V165, P14, DOI [10.1093/aje/kw346, 10.1093/aje/kwj346]