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

Abstract

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.

Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes

“…Quality control steps follow the approach described previously for the OncoArray 5 (Supplementary Note). …”

Genome-Wide Association Studies in Glioma

“…This featured a meta-analysis of six existing GWAS and two new GWAS making use of the Illumina OncoArray (35), in total comprising 12,496 cases and 18,190 controls. The study identified 13 new glioma risk loci, five for GBM at 1p31.3 ( JAK1 ), 11q14.1, 16p13.3 (near MPG ), 16q12.1 ( HEATR3 ) and 22q13.1 ( SLC16A8 ), and 8 for non-GBM glioma at 1q32.1 ( MDM4 ), 1q44 ( AKT3 ), 2q33.3 (near IDH1 ), 3p14.1 ( LRIG1 ), 10q24.33 ( OBFC1 ), 11q21 ( MAML2 ), 14q12 ( AKAP6 ), and 16p13.3 ( LMF1 ).…”

Single-Nucleotide Polymorphisms in Vitamin D–Related Genes May Modify Vitamin D–Breast Cancer Associations

“…Genotyping of a subset of Sister Study participants was conducted using Illumina’s Infinium OncoArray-500K beadchip platform via participation in the GAME-ON consortium (49). The OncoArray panel includes a genome-wide backbone of 230,000 tag SNPs.…”

“…Data cleaning and quality control filtering were conducted by the GAME-ON consortium, with further details described elsewhere (49). After these exclusions, 3,363 Sister Study participants (1829 in sub-cohort [including 67 cases] and 1534 additional cases) provided both genotype and 25(OH)D data.…”