Title: A Sparse Graph-Structured Lasso Mixed Model for Genetic Association with Confounding Correction,
Abstract: While linear mixed model (LMM) has shown a competitive performance in
correcting spurious associations raised by population stratification, family
structures, and cryptic relatedness, more challenges are still to be addressed
regarding the complex structure of genotypic and phenotypic data. For example,
geneticists have discovered that some clusters of phenotypes are more
co-expressed than others. Hence, a joint analysis that can utilize such
relatedness information in a heterogeneous data set is crucial for genetic
modeling.
We proposed the sparse graph-structured linear mixed model (sGLMM) that can
incorporate the relatedness information from traits in a dataset with
confounding correction. Our method is capable of uncovering the genetic
associations of a large number of phenotypes together while considering the
relatedness of these phenotypes. Through extensive simulation experiments, we
show that the proposed model outperforms other existing approaches and can
model correlation from both population structure and shared signals. Further,
we validate the effectiveness of sGLMM in the real-world genomic dataset on two
different species from plants and humans. In Arabidopsis thaliana data, sGLMM
behaves better than all other baseline models for 63.4% traits. We also discuss
the potential causal genetic variation of Human Alzheimer's disease discovered
by our model and justify some of the most important genetic loci.