Analysis of 60 reported glioma risk SNPs replicates published GWAS findings but fails to replicate associations from published candidate-gene studies.

Published

Journal Article

Genomewide association studies (GWAS) and candidate-gene studies have implicated single-nucleotide polymorphisms (SNPs) in at least 45 different genes as putative glioma risk factors. Attempts to validate these associations have yielded variable results and few genetic risk factors have been consistently replicated. We conducted a case-control study of Caucasian glioma cases and controls from the University of California San Francisco (810 cases, 512 controls) and the Mayo Clinic (852 cases, 789 controls) in an attempt to replicate previously reported genetic risk factors for glioma. Sixty SNPs selected from the literature (eight from GWAS and 52 from candidate-gene studies) were successfully genotyped on an Illumina custom genotyping panel. Eight SNPs in/near seven different genes (TERT, EGFR, CCDC26, CDKN2A, PHLDB1, RTEL1, TP53) were significantly associated with glioma risk in the combined dataset (P < 0.05), with all associations in the same direction as in previous reports. Several SNP associations showed considerable differences across histologic subtype. All eight successfully replicated associations were first identified by GWAS, although none of the putative risk SNPs from candidate-gene studies was associated in the full case-control sample (all P values > 0.05). Although several confirmed associations are located near genes long known to be involved in gliomagenesis (e.g., EGFR, CDKN2A, TP53), these associations were first discovered by the GWAS approach and are in noncoding regions. These results highlight that the deficiencies of the candidate-gene approach lay in selecting both appropriate genes and relevant SNPs within these genes.

Full Text

Duke Authors

Cited Authors

  • Walsh, KM; Anderson, E; Hansen, HM; Decker, PA; Kosel, ML; Kollmeyer, T; Rice, T; Zheng, S; Xiao, Y; Chang, JS; McCoy, LS; Bracci, PM; Wiemels, JL; Pico, AR; Smirnov, I; Lachance, DH; Sicotte, H; Eckel-Passow, JE; Wiencke, JK; Jenkins, RB; Wrensch, MR

Published Date

  • February 2013

Published In

Volume / Issue

  • 37 / 2

Start / End Page

  • 222 - 228

PubMed ID

  • 23280628

Pubmed Central ID

  • 23280628

Electronic International Standard Serial Number (EISSN)

  • 1098-2272

Digital Object Identifier (DOI)

  • 10.1002/gepi.21707

Language

  • eng

Conference Location

  • United States