These authors jointly directed the work.
Analysis of 60 Reported Glioma Risk SNPs Replicates Published GWAS Findings but Fails to Replicate Associations From Published Candidate-Gene Studies
Article first published online: 31 DEC 2012
© 2012 WILEY PERIODICALS, INC.
Volume 37, Issue 2, pages 222–228, February 2013
How to Cite
Walsh, K. M., Anderson, E., Hansen, H. M., Decker, P. A., Kosel, M. L., Kollmeyer, T., Rice, T., Zheng, S., Xiao, Y., Chang, J. S., McCoy, L. S., Bracci, P. M., Wiemels, J. L., Pico, A. R., Smirnov, I., Lachance, D. H., Sicotte, H., Eckel-Passow, J. E., Wiencke, J. K., Jenkins, R. B. and Wrensch, M. R. (2013), Analysis of 60 Reported Glioma Risk SNPs Replicates Published GWAS Findings but Fails to Replicate Associations From Published Candidate-Gene Studies. Genet. Epidemiol., 37: 222–228. doi: 10.1002/gepi.21707
- Issue published online: 10 JAN 2013
- Article first published online: 31 DEC 2012
- Manuscript Accepted: 22 NOV 2012
- Manuscript Revised: 13 NOV 2012
- Manuscript Received: 12 SEP 2012
- NIH. Grant Numbers: R25CA112355, R01CA52689, P50CA097257, P50CA108961, P30 CA15083
- National Brain Tumor Foundation
- National Institute of Neurological Disorders and Stroke. Grant Number: RC1NS068222Z
- National Cancer Institute's Surveillance, Epidemiology and End Results. Grant Number: HHSN261201000036C
- Cancer Prevention Institute of California. Grant Number: HHSN261201000035C
- University of Southern California. Grant Number: HHSN261201000034C
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.