Bayesian analysis of longitudinal traits in the Korea Association Resource (KARE) cohort.

Abstract

Various methodologies for the genetic analysis of longitudinal data have been proposed and applied to data from large-scale genome-wide association studies (GWAS) to identify single nucleotide polymorphisms (SNPs) associated with traits of interest and to detect SNP-time interactions. We recently proposed a grid-based Bayesian mixed model for longitudinal genetic data and showed that our Bayesian method increased the statistical power compared to the corresponding univariate method and well detected SNP-time interactions. In this paper, we further analyze longitudinal obesity-related traits such as body mass index, hip circumference, waist circumference, and waist-hip ratio from Korea Association Resource data to evaluate the proposed Bayesian method. We first conducted GWAS analyses of cross-sectional traits and combined the results of GWAS analyses through a meta-analysis based on a trajectory model and a random-effects model. We then applied our Bayesian method to a subset of SNPs selected by meta-analysis to further discover SNPs associated with traits of interest and SNP-time interactions. The proposed Bayesian method identified several novel SNPs associated with longitudinal obesity-related traits, and almost 25% of the identified SNPs had significant p-values for SNP-time interactions.