Rapid research progress in genotyping techniques have allowed large genome-wide association studies. Existing methods often focus on... Show moreRapid research progress in genotyping techniques have allowed large genome-wide association studies. Existing methods often focus on determining associations between single loci and a specific phenotype. However, a particular phenotype is usually the result of complex relationships between multiple loci and the environment. In this paper, we describe a two-stage method for detecting epistasis by combining the traditionally used single-locus search with a search for multiway interactions. Our method is based on an extended version of Fisher’s exact test. To perform this test, a Markov chain is constructed on the space of multidimensional contingency tables using the elements of a Markov basis as moves. We test our method on simulated data and compare it to a two-stage logistic regression method and to a fully Bayesian method, showing that we are able to detect the interacting loci when other methods fail to do so. Finally, we apply our method to a genome-wide data set consisting of 685 dogs and identify epistasis associated with canine hair length for four pairs of single nucleotide polymorphisms (SNPs). Show less
We consider the lattice, L, of all subsets of a multidimensional contingency table and establish the properties of monotonicity and... Show moreWe consider the lattice, L, of all subsets of a multidimensional contingency table and establish the properties of monotonicity and supermodularity for the marginalization function, n(·), on L. We derive from the supermodularity of n(·) some generalized Fr ́echet inequalities comple- menting and extending inequalities of Dobra and Fienberg. Further, we construct new monotonic and supermodular functions from n(·), and we remark on the connection between supermodularity and some correlation inequalities for probability distributions on lattices. We also apply an inequal- ity of Ky Fan to derive a new approach to Fr ́echet inequalities for multidimensional contingency tables. Show less
