Skip to main content
×
Home
    • Aa
    • Aa
  • Access
  • Cited by 2
  • Cited by
    This article has been cited by the following publications. This list is generated based on data provided by CrossRef.

    Kuo, P.H. Chuang, L.C. Liu, J.R. Liu, C.M. Huang, M.C. Lin, S.K. Sunny Sun, H. Hsieh, M.H. Hung, H. and Lu, R.B. 2014. Identification of novel loci for bipolar I disorder in a multi-stage genome-wide association study. Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 51, p. 58.


    Shi, Min Umbach, David M. and Weinberg, Clarice R. 2014. Disentangling Pooled Triad Genotypes for Association Studies. Annals of Human Genetics, Vol. 78, Issue. 5, p. 345.


    ×

Genome-Wide Association Study for Ovarian Cancer Susceptibility Using Pooled DNA

  • Yi Lu (a1), Xiaoqing Chen (a1), Jonathan Beesley (a1), Sharon E. Johnatty (a1), Anna deFazio (a2) (a3), Sandrina Lambrechts (a4), Diether Lambrechts (a5) (a6), Evelyn Despierre (a4), Ignace Vergotes (a4), Jenny Chang-Claude (a7), Rebecca Hein (a7), Stefan Nickels (a7), Shan Wang-Gohrke (a8), Thilo Dörk (a9), Matthias Dürst (a10), Natalia Antonenkova (a11), Natalia Bogdanova (a11) (a12), Marc T. Goodman (a13), Galina Lurie (a13), Lynne R. Wilkens (a13), Michael E. Carney (a14), Ralf Butzow (a15), Heli Nevanlinna (a15), Tuomas Heikkinen (a15), Arto Leminen (a15), Lambertus A. Kiemeney (a16) (a17) (a18), Leon F.A.G. Massuger (a19), Anne M. van Altena (a19), Katja K. Aben (a17) (a18), Susanne Krüger Kjaer (a20), Estrid Høgdall (a20), Allan Jensen (a21), Angela Brooks-Wilson (a22) (a23), Nhu Le (a24), Linda Cook (a25), Madalene Earp (a23), Linda Kelemen (a26), Douglas Easton (a27), Paul Pharoah (a27), Honglin Song (a27), Jonathan Tyrer (a27), Susan Ramus (a28), Usha Menon (a29), Alexandra Gentry-Maharaj (a29), Simon A. Gayther (a28), Elisa V. Bandera (a30) (a31), Sara H. Olson (a31), Irene Orlow (a31), Lorna Rodriguez-Rodriguez (a30), Stuart Macgregor (a1) and Georgia Chenevix-Trench (a1)
  • DOI: http://dx.doi.org/10.1017/thg.2012.38
  • Published online: 13 July 2012
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.

Copyright
Corresponding author
address for correspondence: Stuart Macgregor, Queensland Institute of Medical Research, Locked Bag 2000, Herston, Queensland 4029, Australia. E-mail: stuart.macgregor@qimr.edu.au
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

K. L. Bolton , J. Tyrer , H. Song , S. J. Ramus , M. Notaridou , C. Jones , & S. A. Gayther (2010). Common variants at 19p13 are associated with susceptibility to ovarian cancer. Nature Genetics, 42, 880884.

A. R. Burkey , & P. A. Kanetsky (2009). Development of a novel location-based assessment of sensory symptoms in cancer patients: Preliminary reliability and validity assessment. Journal of Pain and Symptom Management, 37, 848862.

Y. M. Chang , J. A. Newton-Bishop , D. T. Bishop , B. K. Armstrong , V. Bataille , W. Bergman , M. Berwick , P. M. Bracci , J. M. Elwood , M. S. Ernstoff , A. C. Green , N. A. Gruis , E. A. Holly , C. Ingvar , P. A. Kanetsky , M. R. Karagas , Le L. Marchand , R. M. Mackie , H. Olsson , A. Østerlind , T. R. Rebbeck , K. Reich , P. Sasieni , V. Siskind , A. J. Swerdlow , L. Titus-Ernstoff , M. S. Zens , A. Ziegler , & J. H. Barrett (2009). A pooled analysis of melanocytic nevus phenotype and the risk of cutaneous melanoma at different latitudes. International Journal of Cancer, 124, 420428.

J. E. Craig , A. W. Hewitt , A. E. McMellon , A. K. Henders , L. J. Ma , L. Wallace , S. Sharma , K. P. Burdon , P. M. Visscher , G. W. Montgomery , & S. MacGregor (2009). Rapid inexpensive genome-wide association using pooled whole blood. Genome Research, 19, 20752080.

O. Fletcher , & R. S. Houlston (2010). Architecture of inherited susceptibility to common cancer. Nature Reviews Cancer, 10, 353361.

E. L. Goode , G. Chenevix-Trench , H. Song , S. J. Ramus , M. Notaridou , K. Lawrenson , & P. D. Pharoah (2010). A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24. Nature Genetics, 42, 874879.

A. Jawaid , & P. Sham (2009). Impact and quantification of the sources of error in DNA pooling designs. Annals of Human Genetics, 73, 118124.

S. E. Johnatty , J. Beesley , X. Chen , S. Macgregor , D. L. Duffy , A. B. Spurdle , & G. Chenevix-Trench (2010). Evaluation of candidate stromal epithelial cross-talk genes identifies association between risk of serous ovarian cancer and TERT, a cancer susceptibility “hot-spot.” PLoS Genetics, 6, e1001016.

P. A. Kanetsky , N. Mitra , S. Vardhanabhuti , M. Li , D. J. Vaughn , R. Letrero , R. Letrero , S. L. Ciosek , D. R. Doody , L. M. Smith , J. Weaver , A. Albano , C. Chen , J. R. Starr , D. J. Rader , A. K. Godwin , M. P. Reilly , H. Hakonarson , S. M. Schwartz , & K. L. Nathanson (2009). Common variation in KITLG and at 5q31.3 predisposes to testicular germ cell cancer. Nature Genetics, 41, 811815.

S. Le Hellard , S. J. Ballereau , P. M. Visscher , H. S. Torrance , J. Pinson , S. W. Morris , M. L. Thomson , C. A. Semple , W. J. Muir , D. H. Blackwood , D. J. Porteous , & K. L. Evans (2002). SNP genotyping on pooled DNAs: Comparison of genotyping technologies and a semi-automated method for data storage and analysis. Nucleic Acids Research, 30, e74.

P. Lichtenstein , N. V. Holm , P. K. Verkasalo , A. Iliadou , J. Kaprio , M. Koskenvuo , E. Pukkala , A. Skytthe , & K. Hemminki (2000). Environmental and heritable factors in the causation of cancer analyses of cohorts of twins from Sweden, Denmark, and Finland. New England Journal of Medicine, 343, 7885.

Y. Lu , D. P. Dimasi , P. G. Hysi , A. W. Hewitt , K. P. Burdon , T. Toh , J. B. Ruddle , Y. J. Li , P. Mitchell , P. R. Healey , G. W. Montgomery , N. Hansell , T. D. Spector , N. G. Martin , T. L. Young , C. J. Hammond , S. Macgregor , J. E. Craig , & D. A. Mackey (2010). Common genetic variants near the Brittle Cornea Syndrome locus ZNF469 influence the blinding disease risk factor central corneal thickness. PLoS Genetics, 6, e1000947.

S. Macgregor (2007). Most pooling variation in array-based DNA pooling is attributable to array error rather than pool construction error. European Journal of Human Genetics, 15, 501504.

S. Macgregor , P. M. Visscher , & G. Montgomery (2006). Analysis of pooled DNA samples on high density arrays without prior knowledge of differential hybridization rates. Nucleic Acids Research, 34, e55.

S. Macgregor , Z. Z. Zhao , A. Henders , N. G. Martin , G. W. Montgomery , & P. M. Visscher (2008). Highly cost-efficient genome-wide association studies using DNA pools and dense SNP arrays. Nucleic Acids Research, 36, e35.

N. Norton , N. M. Williams , M. C. O'Donovan , & M. J. Owen (2004). DNA pooling as a tool for large-scale association studies in complex traits. Annals of Medicine, 36, 146152.

S. Purcell , B. Neale , K. Todd-Brown , L. Thomas , M. A. Ferreira , D. Bender , J. Maller , P. Sklar , P. I. de Bakker , M. J. Daly , & P. C. Sham (2007). PLINK: A tool set for whole-genome association and population-based linkage analyses. American Journal of Human Genetics, 81, 559575.

P. Sham , J. S. Bader , I. Craig , M. O'Donovan , & M. Owen (2002). DNA pooling: A tool for large-scale association studies. Nature Reviews Genetics, 3, 862871.

H. Song , S. J. Ramus , J. Tyrer , K. L. Bolton , A. Gentry-Maharaj , E. Wozniak , & S. A. Gayther (2009). A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2. Nature Genetics, 41, 9961000.

J. S. Varghese , & D. F. Easton (2010). Genome-wide association studies in common cancers – what have we learnt? Current Opinion in Genetics and Development, 20, 201209.

P. M. Visscher , & Le S. Hellard (2003). Simple method to analyze SNP-based association studies using DNA pools. Genetic Epidemiology, 24, 291296.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Twin Research and Human Genetics
  • ISSN: 1832-4274
  • EISSN: 1839-2628
  • URL: /core/journals/twin-research-and-human-genetics
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords: