Analysis of 60 Reported Glioma Risk SNPs Replicates Published GWAS Findings but Fails to Replicate Associations From Published Candidate-Gene Studies

Kyle M. Walsh, Erik Anderson, Helen M. Hansen, Paul A. Decker, Matt L. Kosel, Thomas Kollmeyer, Terri Rice, Shichun Zheng, Yuanyuan Xiao, Jeffrey S. Chang, Lucie S. Mccoy, Paige M. Bracci, Joe L. Wiemels, Alexander R. Pico, Ivan Smirnov, Daniel H Lachance, Hugues Sicotte, Jeanette E Eckel-Passow, John K. Wiencke, Robert Brian Jenkins & 1 others Margaret R. Wrensch

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)222-228
Number of pages7
JournalGenetic Epidemiology
Volume37
Issue number2
DOIs
StatePublished - Feb 2013

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Glioma
Single Nucleotide Polymorphism
Genes
Genetic Association Studies
erbB-1 Genes
San Francisco
Case-Control Studies

Keywords

  • Candidate-gene
  • Glioma
  • GWAS
  • SNP

ASJC Scopus subject areas

  • Genetics(clinical)
  • Epidemiology

Cite this

Analysis of 60 Reported Glioma Risk SNPs Replicates Published GWAS Findings but Fails to Replicate Associations From Published Candidate-Gene Studies. / Walsh, Kyle M.; Anderson, Erik; Hansen, Helen M.; Decker, Paul A.; Kosel, Matt L.; Kollmeyer, Thomas; Rice, Terri; Zheng, Shichun; Xiao, Yuanyuan; Chang, Jeffrey S.; Mccoy, Lucie S.; Bracci, Paige M.; Wiemels, Joe L.; Pico, Alexander R.; Smirnov, Ivan; Lachance, Daniel H; Sicotte, Hugues; Eckel-Passow, Jeanette E; Wiencke, John K.; Jenkins, Robert Brian; Wrensch, Margaret R.

In: Genetic Epidemiology, Vol. 37, No. 2, 02.2013, p. 222-228.

Research output: Contribution to journalArticle

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 2013, 'Analysis of 60 Reported Glioma Risk SNPs Replicates Published GWAS Findings but Fails to Replicate Associations From Published Candidate-Gene Studies', Genetic Epidemiology, vol. 37, no. 2, pp. 222-228. https://doi.org/10.1002/gepi.21707
Walsh, Kyle M. ; Anderson, Erik ; Hansen, Helen M. ; Decker, Paul A. ; Kosel, Matt L. ; Kollmeyer, Thomas ; Rice, Terri ; Zheng, Shichun ; Xiao, Yuanyuan ; Chang, Jeffrey S. ; Mccoy, Lucie S. ; Bracci, Paige M. ; Wiemels, Joe L. ; Pico, Alexander R. ; Smirnov, Ivan ; Lachance, Daniel H ; Sicotte, Hugues ; Eckel-Passow, Jeanette E ; Wiencke, John K. ; Jenkins, Robert Brian ; Wrensch, Margaret R. / Analysis of 60 Reported Glioma Risk SNPs Replicates Published GWAS Findings but Fails to Replicate Associations From Published Candidate-Gene Studies. In: Genetic Epidemiology. 2013 ; Vol. 37, No. 2. pp. 222-228.
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AU - Kosel, Matt L.

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AU - Chang, Jeffrey S.

AU - Mccoy, Lucie S.

AU - Bracci, Paige M.

AU - Wiemels, Joe L.

AU - Pico, Alexander R.

AU - Smirnov, Ivan

AU - Lachance, Daniel H

AU - Sicotte, Hugues

AU - Eckel-Passow, Jeanette E

AU - Wiencke, John K.

AU - Jenkins, Robert Brian

AU - Wrensch, Margaret R.

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