Epistasis pp 217-255

Part of the Methods in Molecular Biology book series (MIMB, volume 1253) | Cite as

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

  • Carlos Riveros
  • Renato Vimieiro
  • Elizabeth G. Holliday
  • Christopher Oldmeadow
  • Jie Jin Wang
  • Paul Mitchell
  • John Attia
  • Rodney J. Scott
  • Pablo A. Moscato
Protocol

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.

Key words

Epistasis Machine learning Association studies Combinatorial optimization GPU-based methods Gene–environment 

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Carlos Riveros
    • 1
    • 2
  • Renato Vimieiro
    • 1
    • 2
  • Elizabeth G. Holliday
    • 3
    • 4
  • Christopher Oldmeadow
    • 3
    • 4
  • Jie Jin Wang
    • 5
    • 6
  • Paul Mitchell
    • 6
  • John Attia
    • 3
    • 4
  • Rodney J. Scott
    • 1
    • 3
  • Pablo A. Moscato
    • 1
    • 2
  1. 1.Centre for Bioinformatics, Biomarker Discovery, and Information-Based MedicineHunter Medical Research InstituteNew Lambton HeightsAustralia
  2. 2.School of Electrical Engineering and Computer ScienceThe University of NewcastleCallaghanAustralia
  3. 3.School of Medicine and Public HealthThe University of NewcastleCallaghanAustralia
  4. 4.CREDITSS—Clinical Research Design, Information Technology and Statistical Support UnitHunter Medical Research InstituteNew Lambton HeightsAustralia
  5. 5.Centre for Eye Research Australia and Department of OphthalmologyUniversity of MelbourneMelbourneAustralia
  6. 6.Department of Ophthalmology, Centre for Vision Research, Westmead Millennium InstituteUniversity of SydneySydneyAustralia

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