Abstract
Genome-wide association studies have led in the past to the discovery of susceptibility genes for many diseases including cancer and inflammatory conditions. However, a number of these studies did not realise their full potential. A first critical step in developing such large-scale studies is the choice of genotyping array with respect to the study goal. Coverage is the central criterion for array evaluation. We distinguish between estimates of global coverage across the genome, coverage for each chromosome, coverage for selected pathways and the coverage for genes of interest. Here, we focus on inflammatory and immunological pathways and genes relevant for haematopoietic stem cell transplantation. We compared three arrays: the Infinium Global Screening Array-24 v1.0, the Infinium OncoArray-500 K BeadChip and the Infinium PsychArray-24 v1.2 BeadChip. We employed the European population from the 1000 Genomes Project as reference genome. Global coverage was found to range between 12.2 and 14.2% whereas coverage for a selected pathway ranged from 6.2 to 13.2% and gene coverage ranged from 0 to 54.1%. The Global Screening Array outperformed both other arrays in terms of global coverage, for most chromosomes, most considered pathways and most genes. When selecting suitable arrays for a new study, the coverage of pathways or genes of interest should be considered in addition to global coverage. Local coverage should be regarded when discussing association findings inconsistent across studies and can be useful in data analysis and decision making for additional genotyping.
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Acknowledgements
This project was conducted as collaboration with the Transdisciplinary Research of Cancer in Lung and the International Lung Cancer Consortium (TRICL/ILCCO). We also wish to thank Andrew Entwistle for proofreading the paper.
Funding
The National Institutes of Health (7U19CA203654-02/114564-5111078 Integrative Analysis of Lung Cancer Etiology and Risk) supported this work.
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Tozzi, V., Rosenberger, A., Kube, D. et al. Global, pathway and gene coverage of three Illumina arrays with respect to inflammatory and immune-related pathways. Eur J Hum Genet 27, 1716–1723 (2019). https://doi.org/10.1038/s41431-019-0441-2
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DOI: https://doi.org/10.1038/s41431-019-0441-2
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