The OncoArray Consortium: A Network for Understanding the Genetic Architecture of Common Cancers
Authors: Amos Christopher I. , Dennis Joe , Wang Zhaoming , Byun Jinyoung , Schumacher Fredrick R. , Gayther Simon A. , Casey Graham , Hunter David J. , Sellers Thomas A. , Gruber Stephen B. , Dunning Alison M. , Michailidou Kyriaki , Fachal Laura , Doheny Kimberly , Spurdle Amanda B. , Li Yafang , Xiao Xiangjun , Romm Jane , Pugh Elizabeth , Coetzee Gerhard A. , Hazelett Dennis J. , Bojesen Stig E. , Caga-Anan Charlisse , Haiman Christopher A. , Kamal Ahsan , Luccarini Craig , Tessier Daniel , Vincent Daniel , Bacot François , Van Den Berg David J. , Nelson Stefanie , Demetriades Stephen , Goldgar David E. , Couch Fergus J. , Forman Judith L. , Giles Graham G. , Conti David V. , Bickeböller Heike , Risch Angela , Waldenberger Melanie , Brüske-Hohlfeld Irene , Hicks Belynda D. , Ling Hua , McGuffog Lesley , Lee Andrew , Kuchenbaecker Karoline , Soucy Penny , Manz Judith , Cunningham Julie M. , Butterbach Katja , Kote-Jarai Zsofia , Kraft Peter , FitzGerald Liesel , Lindström Sara , Adams Marcia , McKay James D. , Phelan Catherine M. , Benlloch Sara , Kelemen Linda E. , Brennan Paul , Riggan Marjorie , O'Mara Tracy A. , Shen Hongbing , Shi Yongyong , Thompson Deborah J. , Goodman Marc T. , Nielsen Sune F. , Berchuck Andrew , Laboissiere Sylvie , Schmit Stephanie L. , Shelford Tameka , Edlund Christopher K. , Taylor Jack A. , Field John K. , Park Sue K. , Offit Kenneth , Thomassen Mads , Schmutzler Rita , Ottini Laura , Hung Rayjean J. , Marchini Jonathan , Amin Al Olama Ali , Peters Ulrike , Eeles Rosalind A. , Seldin Michael F. , Gillanders Elizabeth , Seminara Daniela , Antoniou Antonis C. , Pharoah Paul D.P. , Chenevix-Trench Georgia , Chanock Stephen J. , Simard Jacques , Easton Douglas F. 
Published: October 2016

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.