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 language | English (US) |
|---|---|
| Pages (from-to) | 222-228 |
| Number of pages | 7 |
| Journal | Genetic Epidemiology |
| Volume | 37 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 2013 |
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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 journal › Article
}
TY - JOUR
T1 - Analysis of 60 Reported Glioma Risk SNPs Replicates Published GWAS Findings but Fails to Replicate Associations From Published Candidate-Gene Studies
AU - Walsh, Kyle M.
AU - Anderson, Erik
AU - Hansen, Helen M.
AU - Decker, Paul A.
AU - Kosel, Matt L.
AU - Kollmeyer, Thomas
AU - Rice, Terri
AU - Zheng, Shichun
AU - Xiao, Yuanyuan
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.
PY - 2013/2
Y1 - 2013/2
N2 - 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.
AB - 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.
KW - Candidate-gene
KW - Glioma
KW - GWAS
KW - SNP
UR - http://www.scopus.com/inward/record.url?scp=84872401601&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84872401601&partnerID=8YFLogxK
U2 - 10.1002/gepi.21707
DO - 10.1002/gepi.21707
M3 - Article
C2 - 23280628
AN - SCOPUS:84872401601
VL - 37
SP - 222
EP - 228
JO - Genetic Epidemiology
JF - Genetic Epidemiology
SN - 0741-0395
IS - 2
ER -