• Open Access

Mixture modelling as an exploratory framework for genotype–trait associations


Andrea S. Foulkes, Division of Biostatistics and Epidemiology, University of Massachusetts, Arnold House, 715 North Pleasant Street, Amherst, MA 01003, USA.
E-mail: foulkes@schoolph.umass.edu


Summary.  We propose a mixture modelling framework for both identifying and exploring the nature of genotype–trait associations. This framework extends the classical mixed effects modelling approach for this setting by incorporating a Gaussian mixture distribution for random genotype effects. The primary advantages of this paradigm over existing approaches include that the mixture modelling framework addresses the degrees-of-freedom challenge that is inherent in application of the usual fixed effects analysis of covariance, relaxes the restrictive single normal distribution assumption of the classical mixed effects models and offers an exploratory framework for discovery of underlying structure across multiple genetic loci. An application to data arising from a study of antiretroviral-associated dyslipidaemia in human immunodeficiency virus infection is presented. Extensive simulations studies are also implemented to investigate the performance of this approach.