title: Linkage Disequilibrium in Genetic Association Studies Improves the Performance of Grammatical Evolution Neural Networks.
abstract: One of the most important goals in genetic epidemiology is the identification of genetic factors/features that predict complex diseases. The ubiquitous nature of gene-gene interactions in the underlying etiology of common diseases creates an important analytical challenge, spurring the introduction of novel, computational approaches. One such method is a grammatical evolution neural network (GENN) approach. GENN has been shown to have high power to detect such interactions in simulation studies, but previous studies have ignored an important feature of most genetic data: linkage disequilibrium (LD). LD describes the non-random association of alleles not necessarily on the same chromosome. This results in strong correlation between variables in a dataset, which can complicate analysis. In the current study, data simulations with a range of LD patterns are used to assess the impact of such correlated variables on the performance of GENN. Our results show that not only do patterns of strong LD not decrease the power of GENN to detect genetic associations, they actually increase its power.
authors.affiliation: Center for Human Genetics Research, Department of Molecular Physiology & Biophysics, Vanderbilt University, Nashville, TN, USA 37232.
authors.forename: Alison A
authors.initials: AA
authors.lastname: Motsinger
authors.forename: David M
authors.initials: DM
authors.lastname: Reif
authors.forename: Theresa J
authors.initials: TJ
authors.lastname: Fanelli
authors.forename: Anna C
authors.initials: AC
authors.lastname: Davis
authors.forename: Marylyn D
authors.initials: MD
authors.lastname: Ritchie