title: A nonparametric regression method for multiple longitudinal phenotypes using multivariate adaptive splines.
abstract: In genetic studies of complex diseases, particularly mental illnesses, and behavior disorders, two distinct characteristics have emerged in some data sets. First, genetic data sets are collected with a large number of phenotypes that are potentially related to the complex disease under study. Second, each phenotype is collected from the same subject repeatedly over time. In this study, we present a nonparametric regression approach to study multivariate and time-repeated phenotypes together by using the technique of the multivariate adaptive regression splines for analysis of longitudinal data (MASAL), which makes it possible to identify genes, gene-gene and gene-environment, including time, interactions associated with the phenotypes of interest. Furthermore, we propose a permutation test to assess the associations between the phenotypes and selected markers. Through simulation, we demonstrate that our proposed approach has advantages over the existing methods that examine each longitudinal phenotype separately or analyze the summarized values of phenotypes by compressing them into one-time-point phenotypes. Application of the proposed method to the Framingham Heart Study illustrates that the use of multivariate longitudinal phenotypes enhanced the significance of the association test.
authors.affiliation: Key Laboratory for Applied Statistics of MOE, School of Mathematics and Statistics, Northeast Normal University, Changchun 130024, China ; Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520-8034, USA.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520-8034, USA.
authors.forename: Heping
authors.initials: H
authors.lastname: Zhang
keywords: Multivariate phenotypes; genetic association test; longitudinal data analysis; multivariate adaptive regression splines