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Epistasis pp 217–255Cite as

Identification of Genome-Wide SNP–SNP and SNP–Clinical Boolean Interactions in Age-Related Macular Degeneration

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1253))

Abstract

We propose here a methodology to uncover modularities in the network of SNP–SNP interactions most associated with disease. We start by computing all possible Boolean binary SNP interactions across the whole genome. By constructing a weighted graph of the most relevant interactions and via a combinatorial optimization approach, we find the most highly interconnected SNPs. We show that the method can be easily extended to find SNP/environment interactions. Using a modestly sized GWAS dataset of age-related macular degeneration (AMD), we identify a group of only 19 SNPs, which include those in previously reported regions associated to AMD. We also uncover a larger set of loci pointing to a matrix of key processes and functions that are affected. The proposed integrative methodology extends and overlaps traditional statistical analysis in a natural way. Combinatorial optimization techniques allow us to find the kernel of the most central interactions, complementing current methods of GWAS analysis and also enhancing the search for gene–environment interaction.

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Acknowledgements

This work was supported by the National Health and Medical Research Council [Grant 512423 Genes and environment in the risk of early age-related macular degeneration: a population-based case-control study, to J.J.W., P.M., and J.A., and fellowship scheme to E.G.H.]. We are grateful to Katrina Bogan for her careful revision of the manuscript.

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Authors and Affiliations

  1. Centre for Bioinformatics, Biomarker Discovery, and Information-Based Medicine, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia

    Carlos Riveros, Renato Vimieiro, Rodney J. Scott & Pablo A. Moscato

  2. School of Electrical Engineering and Computer Science, The University of Newcastle, Level 3 Pod – 3020, HMRI Building, Lot 1, Kookaburra Circuit, Callaghan, NSW, 2305, Australia

    Carlos Riveros, Renato Vimieiro & Pablo A. Moscato

  3. School of Medicine and Public Health, The University of Newcastle, Callaghan, NSW, Australia

    Elizabeth G. Holliday, Christopher Oldmeadow, John Attia & Rodney J. Scott

  4. CREDITSS—Clinical Research Design, Information Technology and Statistical Support Unit, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia

    Elizabeth G. Holliday, Christopher Oldmeadow & John Attia

  5. Centre for Eye Research Australia and Department of Ophthalmology, University of Melbourne, Melbourne, Australia

    Jie Jin Wang

  6. Department of Ophthalmology, Centre for Vision Research, Westmead Millennium Institute, University of Sydney, Sydney, Australia

    Jie Jin Wang & Paul Mitchell

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  1. Carlos Riveros
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  7. John Attia
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  9. Pablo A. Moscato
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Correspondence to Carlos Riveros .

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  1. Department of Genetics, Institute of Quantitative Biomedical Sciences, Geisel School of Medicine, Hanover, New Hampshire, USA

    Jason H. Moore

  2. Department of Genetics, Institute of Quantitative Biomedical Sciences, Geisel School of Medicine, Hanover, New Hampshire, USA

    Scott M. Williams

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Riveros, C. et al. (2015). Identification of Genome-Wide SNP–SNP and SNP–Clinical Boolean Interactions in Age-Related Macular Degeneration. In: Moore, J., Williams, S. (eds) Epistasis. Methods in Molecular Biology, vol 1253. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2155-3_12

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  • DOI: https://doi.org/10.1007/978-1-4939-2155-3_12

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