Abstract

Precise prediction for genetic architecture of complex traits is impeded by the limited understanding on genetic effects of complex traits, especially on gene-by-gene (GxG) and gene-by-environment (GxE) interaction. In the past decades, an explosion of high throughput technologies enables omics studies at multiple levels (such as genomics, transcriptomics, proteomics, and metabolomics). The analyses of large omics data, especially two-loci interaction analysis, are very time intensive. Integrating the diverse omics data and environmental effects in the analyses also remain challenges. We proposed mixed linear model approaches using GPU (Graphic Processing Unit) computation to simultaneously dissect various genetic effects. Analyses can be performed for estimating genetic main effects, GxG epistasis effects, and GxE environment interaction effects on large-scale omics data for complex traits, and for estimating heritability of specific genetic effects. Both mouse data analyses and Monte Carlo simulations demonstrated that genetic effects and environment interaction effects could be unbiasedly estimated with high statistical power by using the proposed approaches.

Highlights

  • Both natural and experimental populations harbor an array of phenotypic variations because of the complicate genetic architecture underlying quantitative traits

  • By analyzing mouse datasets on anxiety and Monte Carlo simulations for linkage mapping of quantitative trait locus (QTL), association mapping of quantitative trait SNP (QTS) and QTTs, we demonstrated that unbiased estimation could be obtained for genetic effects of causal genes

  • Animals of 71 BXD recombinant inbred (RI) strains, 60 to 120 days old, were used. These strains were derived by crossing C57BL/6J (B6) and DBA/2J (D2) strains in the 1970s (BXD1-32; 26 strains) and 1990s (BXD33-42; 9 strains)[40]

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Summary

Introduction

Both natural and experimental populations harbor an array of phenotypic variations because of the complicate genetic architecture underlying quantitative traits. Our approaches consist of four steps in statistical analyses: (1) one-dimension search for individual loci; (2) exhaustive two-dimension search for epistasis loci; (3) stepwise search for fitting a full genetic model, including candidate loci with main effects, epistasis, and GxE interaction; and (4) estimating gene effects of individual and epistasis loci detected in previous process by method of Monte Carlo Markov Chain via Gibbs Sampling[24,37]. All these processes have been implemented in a GPU-based mapping software, named QTXNetwork. The package QTXNetwork can be downloaded at the following website http://ibi.zju.edu.cn/software/QTXNetwork

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