Title: Genome-wide association study for ovarian cancer susceptibility using pooled DNA
Authors: Chen, Xiaoqing
Beesley, Jonathan
Johnatty, Sharon E
Defazio, Anna
Australian Ovarian Cancer Study (AOCS) Study Group
Lambrechts, Sandrina
Lambrechts, Diether
Despierre, Evelyn ×
Vergotes, Ignace
Chang-Claude, Jenny
Hein, Rebecca
Nickels, Stefan
Wang-Gohrke, Shan
Dörk, Thilo
Dürst, Matthias
Antonenkova, Natalia
Bogdanova, Natalia
Goodman, Marc T
Lurie, Galina
Wilkens, Lynne R
Carney, Michael E
Butzow, Ralf
Nevanlinna, Heli
Heikkinen, Tuomas
Leminen, Arto
Kiemeney, Lambertus A
Massuger, Leon F A G
van Altena, Anne M
Aben, Katja K
Kjaer, Susanne Krüger
Høgdall, Estrid
Jensen, Allan
Brooks-Wilson, Angela
Cook, Linda
Earp, Madalene
Kelemen, Linda
Easton, Douglas
Pharoah, Paul
Song, Honglin
Tyrer, Jonathan
Ramus, Susan
Menon, Usha
Gentry-Maharaj, Alexandra
Gayther, Simon A
Bandera, Elisa V
Olson, Sara H
Orlow, Irene
Rodriguez-Rodriguez, Lorna
Macgregor, Stuart
Chenevix-Trench, Georgia #
Issue Date: Oct-2012
Series Title: Twin Research and Human Genetics vol:15 issue:5 pages:615-623
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.
ISSN: 1832-4274
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Translational Genetics (Vesalius Research Center) (+)
Gynaecological Oncology
× corresponding author
# (joint) last author

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