Genome-wide association study for ovarian cancer susceptibility using pooled DNA.
Twin Res Hum Genet
; 15(5): 615-623, 2012 Oct.
Article
in En
| MEDLINE
| ID: mdl-22794196
ABSTRACT
Recent Genome-Wide Association Studies (GWAS) have identified four low-penetrance ovarian cancer susceptibility loci. We hypothesized that further moderate- or low-penetrance variants exist among the subset of single-nucleotide polymorphisms (SNPs) not well tagged by the genotyping arrays used in the previous studies, which would account for some of the remaining risk. We therefore conducted a time- and cost-effective stage 1 GWAS on 342 invasive serous cases and 643 controls genotyped on pooled DNA using the high-density Illumina 1M-Duo array. We followed up 20 of the most significantly associated SNPs, which are not well tagged by the lower density arrays used by the published GWAS, and genotyping them on individual DNA. Most of the top 20 SNPs were clearly validated by individually genotyping the samples used in the pools. However, none of the 20 SNPs replicated when tested for association in a much larger stage 2 set of 4,651 cases and 6,966 controls from the Ovarian Cancer Association Consortium. Given that most of the top 20 SNPs from pooling were validated in the same samples by individual genotyping, the lack of replication is likely to be due to the relatively small sample size in our stage 1 GWAS rather than due to problems with the pooling approach. We conclude that there are unlikely to be any moderate or large effects on ovarian cancer risk untagged by less dense arrays. However, our study lacked power to make clear statements on the existence of hitherto untagged small-effect variants.
Full text:
1
Database:
MEDLINE
Main subject:
Ovarian Neoplasms
/
Genetic Predisposition to Disease
/
Polymorphism, Single Nucleotide
/
Genome-Wide Association Study
Type of study:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Aged
/
Female
/
Humans
/
Middle aged
Country/Region as subject:
Oceania
Language:
En
Journal:
Twin Res Hum Genet
Journal subject:
GENETICA MEDICA
Year:
2012
Type:
Article
Affiliation country:
Australia