A time-varying group sparse additive model for genome-wide association studies of dynamic complex traits

Abstract

MOTIVATION: Despite the widespread popularity of genome-wide association studies (GWAS) for genetic mapping of complex traits, most existing GWAS methodologies are still limited to the use of static phenotypes measured at a single time point. In this work, we propose a new method for association mapping that considers dynamic phenotypes measured at a sequence of time points. Our approach relies on the use of Time-Varying Group Sparse Additive Models (TV-GroupSpAM) for high-dimensional, functional regression. RESULTS: This new model detects a sparse set of genomic loci that are associated with trait dynamics, and demonstrates increased statistical power over existing methods. We evaluate our method via experiments on synthetic data and perform a proof-of-concept analysis for detecting single nucleotide polymorphisms associated with two phenotypes used to assess asthma severity: forced vital capacity, a sensitive measure of airway obstruction and bronchodilator response, which measures lung response to bronchodilator drugs. AVAILABILITY AND IMPLEMENTATION: Source code for TV-GroupSpAM freely available for download at http://www.cs.cmu.edu/~mmarchet/projects/tv_group_spam, implemented in MATLAB. CONTACT: epxing@cs.cmu.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.