Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
22794196
TITLE
Genome-wide association study for ovarian cancer susceptibility using pooled DNA.
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.
DATE PUBLISHED
2012 Oct
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2012/07/17 06:00
pubmed 2012/07/17 06:00
medline 2013/04/05 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Lu Y Lu Yi Y Queensland Institute of Medical Research, Brisbane, Australia.
Chen X Chen Xiaoqing X Queensland Institute of Medical Research, Brisbane, Australia.
Beesley J Beesley Jonathan J Queensland Institute of Medical Research, Brisbane, Australia.
Johnatty SE Johnatty Sharon E SE Queensland Institute of Medical Research, Brisbane, Australia.
deFazio A deFazio Anna A Westmead Institute for Cancer Research, Westmead Hospital, Sydney, Australia.
AOCS Study group
Lambrechts S Lambrechts Sandrina S Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, University Hospital Leuven, University of Leuven, Leuven, Belgium.
Lambrechts D Lambrechts Diether D Vesalius Research Center, University of Leuven, Belgium.
Despierre E Despierre Evelyn E Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, University Hospital Leuven, University of Leuven, Leuven, Belgium.
Vergotes I Vergotes Ignace I Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, University Hospital Leuven, University of Leuven, Leuven, Belgium.
Chang-Claude J Chang-Claude Jenny J Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Hein R Hein Rebecca R Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Nickels S Nickels Stefan S Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Wang-Gohrke S Wang-Gohrke Shan S Department of Obstetrics and Gynecology, University of Ulm, Ulm, Germany.
Dörk T Dörk Thilo T Hannover Medical School, Gynaecology Research Unit, Hannover, Germany.
Dürst M Dürst Matthias M Friedrich Schiller University, Dept. of Gynaecology, Jena, Germany.
Antonenkova N Antonenkova Natalia N Byelorussian Institute for Oncology and Medical Radiology Aleksandrov N.N., Minsk, Belarus.
Bogdanova N Bogdanova Natalia N Hannover Medical School, Clinics of Radiation Oncology, Hannover, Germany.
Goodman MT Goodman Marc T MT Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, United States.
Lurie G Lurie Galina G Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, United States.
Wilkens LR Wilkens Lynne R LR Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, United States.
Carney ME Carney Michael E ME Department of Obstetrics and Gynecology, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, United States.
Butzow R Butzow Ralf R Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland.
Nevanlinna H Nevanlinna Heli H Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland.
Heikkinen T Heikkinen Tuomas T Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland.
Leminen A Leminen Arto A Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland.
Kiemeney LA Kiemeney Lambertus A LA Comprehensive Cancer Center, The Netherlands Location Nijmegen, Nijmegen, the Netherlands.
Massuger LFAG Massuger Leon F A G LFAG Department of Gynaecology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
van Altena AM van Altena Anne M AM Department of Gynaecology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
Aben KK Aben Katja K KK Comprehensive Cancer Center, The Netherlands Location Nijmegen, Nijmegen, the Netherlands.
Kjaer SK Kjaer Susanne Krüger SK Dept. of Viruses, Hormones and Cancer, Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark.
Høgdall E Høgdall Estrid E Dept. of Viruses, Hormones and Cancer, Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark.
Jensen A Jensen Allan A Dept. of Gynecology, Juliane Marie Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Brooks-Wilson A Brooks-Wilson Angela A Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada.
Le N Le Nhu N Cancer Control Research, BC Cancer Agency, Vancouver, BC, Canada.
Cook L Cook Linda L Division of Epidemiology and Biostatistics, University of New Mexico, Albuquerque, New Mexico, USA.
Earp M Earp Madalene M Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada.
Kelemen L Kelemen Linda L Alberta Health Services-Cancer Care, Calgary, AB, Canada.
Easton D Easton Douglas D Departments of Oncology and Public Health and Primary Care, University of Cambridge, UK.
Pharoah P Pharoah Paul P Departments of Oncology and Public Health and Primary Care, University of Cambridge, UK.
Song H Song Honglin H Departments of Oncology and Public Health and Primary Care, University of Cambridge, UK.
Tyrer J Tyrer Jonathan J Departments of Oncology and Public Health and Primary Care, University of Cambridge, UK.
Ramus S Ramus Susan S Department of Preventive Medicine, Keck School of Medicine, University of Southern California.
Menon U Menon Usha U Gynaecological Oncology Unit, UCL EGA Institute for Women's Health, University College London, UK.
Gentry-Maharaj A Gentry-Maharaj Alexandra A Gynaecological Oncology Unit, UCL EGA Institute for Women's Health, University College London, UK.
Gayther SA Gayther Simon A SA Department of Preventive Medicine, Keck School of Medicine, University of Southern California.
Bandera EV Bandera Elisa V EV Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Olson SH Olson Sara H SH Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Orlow I Orlow Irene I Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Rodriguez-Rodriguez L Rodriguez-Rodriguez Lorna L The Cancer Institute of New Jersey, New Brunswick, NJ, USA.
Macgregor S Macgregor Stuart S Queensland Institute of Medical Research, Brisbane, Australia.
Chenevix-Trench G Chenevix-Trench Georgia G Queensland Institute of Medical Research, Brisbane, Australia.
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Bowtell D D
Chenevix-Trench G G
deFazio A A
Gertig D D
Green A A
Webb P M PM
JOURNAL
VOLUME: 15
ISSUE: 5
TITLE: Twin research and human genetics : the official journal of the International Society for Twin Studies
ISOABBREVIATION: Twin Res Hum Genet
YEAR: 2012
MONTH: Oct
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 1832-4274
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Twin Res Hum Genet
COUNTRY: England
ISSNLINKING: 1832-4274
NLMUNIQUEID: 101244624
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
N01-CN-55424 NCI NIH HHS United States
R01 CA058598 NCI NIH HHS United States
K22 CA138563 NCI NIH HHS United States
N01-PC-67001 NCI NIH HHS United States
R01CA83918 NCI NIH HHS United States
A490/10124 Cancer Research UK United Kingdom
R01 CA083918 NCI NIH HHS United States
N01-PC-95001-20 NCI NIH HHS United States
R01 CA58598 NCI NIH HHS United States
A490/10119 Cancer Research UK United Kingdom
K07CA095666 NCI NIH HHS United States
K22CA138563 NCI NIH HHS United States
10119 Cancer Research UK United Kingdom
Department of Health United Kingdom
K07 CA095666 NCI NIH HHS United States
P30 CA071789 NCI NIH HHS United States
10124 Cancer Research UK United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Aged
Australia
Case-Control Studies
Female
Genetic Predisposition to Disease
Genome-Wide Association Study methods
Humans methods
Middle Aged methods
Ovarian Neoplasms genetics
Polymorphism, Single Nucleotide genetics
Reproducibility of Results genetics
Sample Size genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
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