Login / Signup

Fast and flexible linear mixed models for genome-wide genetics.

Daniel E RuncieLorin Crawford
Published in: PLoS genetics (2019)
Linear mixed effect models are powerful tools used to account for population structure in genome-wide association studies (GWASs) and estimate the genetic architecture of complex traits. However, fully-specified models are computationally demanding and common simplifications often lead to reduced power or biased inference. We describe Grid-LMM (https://github.com/deruncie/GridLMM), an extendable algorithm for repeatedly fitting complex linear models that account for multiple sources of heterogeneity, such as additive and non-additive genetic variance, spatial heterogeneity, and genotype-environment interactions. Grid-LMM can compute approximate (yet highly accurate) frequentist test statistics or Bayesian posterior summaries at a genome-wide scale in a fraction of the time compared to existing general-purpose methods. We apply Grid-LMM to two types of quantitative genetic analyses. The first is focused on accounting for spatial variability and non-additive genetic variance while scanning for QTL; and the second aims to identify gene expression traits affected by non-additive genetic variation. In both cases, modeling multiple sources of heterogeneity leads to new discoveries.
Keyphrases
  • genome wide
  • dna methylation
  • gene expression
  • copy number
  • single cell
  • high resolution
  • genome wide association
  • drinking water
  • machine learning
  • deep learning
  • neural network
  • high density
  • case control