Identification of genome-wide SNP-SNP and SNP-clinical Boolean interactions in age-related macular degeneration.
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.
Centre for Bioinformatics, Biomarker Discovery, and Information-Based Medicine, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia, carlos.riveros@newcastle.edu.au.
Carlos
C
Riveros
Renato
R
Vimieiro
Elizabeth G
EG
Holliday
Christopher
C
Oldmeadow
Jie Jin
JJ
Wang
Paul
P
Mitchell
John
J
Attia
Rodney J
RJ
Scott
Pablo A
PA
Moscato
D059647:Gene-Environment Interaction; D055106:Genome-Wide Association Study; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*; D009716:Numerical Analysis, Computer-Assisted; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*