- Title
- Identification of genome-wide SNP-SNP and SNP-clinical Boolean interactions in age-related macular degeneration
- Creator
- Riveros, Carlos; Vimieiro, Renato; Holliday, Elizabeth G.; Oldmeadow, Christopher; Wang, Jie Jin; Mitchell, Paul; Attia, John; Scott, Rodney J.; Moscato, Pablo A.
- Relation
- Epistasis: Methods and Protocols p. 217-255
- Publisher Link
- http://dx.doi.org/10.1007/978-1-4939-2155-3_12
- Publisher
- Springer
- Resource Type
- book chapter
- Date
- 2015
- Description
- 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.
- Subject
- epistasis; machine learning; association studies; combinatorial optimization; GPU-based methods; gene-environment
- Identifier
- http://hdl.handle.net/1959.13/1309978
- Identifier
- uon:21967
- Identifier
- ISBN:9781493921546
- Language
- eng
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