The OncoArray Consortium: A Network for Understanding the Genetic Architecture of Common Cancers

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Christopher I Amos, Joe Dennis, Zhaoming Wang, Jinyoung Byun, Fredrick R Schumacher, Simon A Gayther, Graham Casey, David J Hunter, Thomas A Sellers, Stephen B Gruber, Alison M Dunning, Kyriaki Michailidou, Laura Fachal, Kimberly Doheny, Amanda B Spurdle, Yafang Li, Xiangjun Xiao, Jane Romm, Elizabeth Pugh, Gerhard A Coetzee & 73 others Dennis J Hazelett, Stig E Bojesen, Charlisse Caga-Anan, Christopher A Haiman, Ahsan Kamal, Craig Luccarini, Daniel C Tessier, Daniel Vincent, François Bacot, David J Van Den Berg, Stefanie Nelson, Stephen Demetriades, David E Goldgar, Fergus J Couch, Judith L Forman, Graham Giles, David V Conti, Heike Bickeböller, Angela Risch, Melanie Waldenberger, Irene Brüske-Hohlfeld, Belynda D Hicks, Hua Ling, Lesley McGuffog, Andrew Lee, Karoline B Kuchenbaecker, Penny Soucy, Judith Manz, Julie M Cunningham, Katja Butterbach, Zsofia Kote-Jarai, Peter Kraft, Liesel Fitzgerald, Sara Lindström, Marcia Adams, James D McKay, Catherine M Phelan, Sara Benlloch, Linda E Kelemen, Paul Brennan, Marjorie Riggan, Tracy A O'Mara, Hongbing Shen, Yongyong Shi, Deborah J Thompson, Marc T Goodman, Sune F Nielsen, Andrew Berchuck, Sylvie Laboissiere, Stephanie L Schmit, Tameka Shelford, Christopher K Edlund, Jack A Taylor, John K Field, Sue K Park, Kenneth Offit, Mads Thomassen, Rita Schmutzler, Laura Ottini, Rayjean J Hung, Jonathan L Marchini, Ali Amin Al Olama, Ulrike Peters, Rosalind A Eeles, Michael F Seldin, Elizabeth Gillanders, Daniela Seminara, Antonis C Antoniou, Paul P D Pharoah, Georgia Chenevix-Trench, Stephen J Chanock, Jacques Simard, Douglas F Easton

BACKGROUND: Common cancers develop through a multistep process often including inherited susceptibility. Collaboration among multiple institutions, and funding from multiple sources, has allowed the development of an inexpensive genotyping microarray, the OncoArray. The array includes a genome-wide backbone, comprising 230,000 SNPs tagging most common genetic variants, together with dense mapping of known susceptibility regions, rare variants from sequencing experiments, pharmacogenetic markers, and cancer-related traits.

METHODS: The OncoArray can be genotyped using a novel technology developed by Illumina to facilitate efficient genotyping. The consortium developed standard approaches for selecting SNPs for study, for quality control of markers, and for ancestry analysis. The array was genotyped at selected sites and with prespecified replicate samples to permit evaluation of genotyping accuracy among centers and by ethnic background.

RESULTS: The OncoArray consortium genotyped 447,705 samples. A total of 494,763 SNPs passed quality control steps with a sample success rate of 97% of the samples. Participating sites performed ancestry analysis using a common set of markers and a scoring algorithm based on principal components analysis.

CONCLUSIONS: Results from these analyses will enable researchers to identify new susceptibility loci, perform fine-mapping of new or known loci associated with either single or multiple cancers, assess the degree of overlap in cancer causation and pleiotropic effects of loci that have been identified for disease-specific risk, and jointly model genetic, environmental, and lifestyle-related exposures.

IMPACT: Ongoing analyses will shed light on etiology and risk assessment for many types of cancer. Cancer Epidemiol Biomarkers Prev; 26(1); 126-35. ©2016 AACR.

Original languageEnglish
JournalCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume26
Issue number1
Pages (from-to)126-135
Number of pages10
ISSN1055-9965
DOIs
Publication statusPublished - Jan 2017

    Research areas

  • Journal Article

ID: 176010746