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Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk.
Nat. Genet. 46, 731-735 (2014)
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.
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Times Cited
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Anmerkungen
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Genome-wide Association; Susceptibility Loci; Promoter Mutations; Cardiovascular-disease; Colorectal-cancer; Glioblastoma; Metaanalysis; Pathways; Melanoma; Humans
Sprache
englisch
Veröffentlichungsjahr
2014
HGF-Berichtsjahr
2014
ISSN (print) / ISBN
1061-4036
e-ISSN
1546-1718
Zeitschrift
Nature Genetics
Quellenangaben
Band: 46,
Heft: 7,
Seiten: 731-735
Verlag
Nature Publishing Group
Verlagsort
New York, NY
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Genetic Epidemiology (IGE)
Institute of Epidemiology (EPI)
Institute of Epidemiology (EPI)
POF Topic(s)
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30202 - Environmental Health
30202 - Environmental Health
Forschungsfeld(er)
Genetics and Epidemiology
PSP-Element(e)
G-504100-001
G-504091-001
G-504000-001
G-504000-007
G-504091-001
G-504000-001
G-504000-007
DOI
10.1038/ng.3004
WOS ID
WOS:000338093800015
Erfassungsdatum
2014-07-28