Title
Efficient network-guided multi-locus association mapping with graph cuts.
Abstract
Motivation: As an increasing number of genome-wide association studies reveal the limitations of the attempt to explain phenotypic heritability by single genetic loci, there is a recent focus on associating complex phenotypes with sets of genetic loci. Although several methods for multi-locus mapping have been proposed, it is often unclear how to relate the detected loci to the growing knowledge about gene pathways and networks. The few methods that take biological pathways or networks into account are either restricted to investigating a limited number of predetermined sets of loci or do not scale to genome-wide settings. Results: We present SConES, a new efficient method to discover sets of genetic loci that are maximally associated with a phenotype while being connected in an underlying network. Our approach is based on a minimum cut reformulation of the problem of selecting features under sparsity and connectivity constraints, which can be solved exactly and rapidly. SConES outperforms state-of-the-art competitors in terms of runtime, scales to hundreds of thousands of genetic loci and exhibits higher power in detecting causal SNPs in simulation studies than other methods. On flowering time phenotypes and genotypes from Arabidopsis thaliana, SConES detects loci that enable accurate phenotype prediction and that are supported by the literature.
Year
DOI
Venue
2013
10.1093/bioinformatics/btt238
BIOINFORMATICS
Keywords
Field
DocType
genetic loci,phenotype,genome wide association study,genotype
Cut,Association mapping,Heritability,Computer science,Minimum cut,Genome-wide association study,Genetic association,Single-nucleotide polymorphism,Bioinformatics,Locus (genetics)
Journal
Volume
Issue
ISSN
29
13
1367-4803
Citations 
PageRank 
References 
16
0.80
16
Authors
5
Name
Order
Citations
PageRank
Chloé-Agathe Azencott1714.72
Dominik Grimm2324.32
Mahito Sugiyama37713.27
Kawahara, Yoshinobu431731.30
Karsten M. Borgwardt52799155.36