Integrating Co-Expression Networks with GWAS to Detect Causal Genes For Agronomically Important Traits

Abstract

The recent availability of high-throughput technologies in agricultural species provides an opportunity to advance our understanding of complex, agronomically important traits. Genome wide association studies (GWAS) have identified thousands of loci linked to these traits; however in most cases the causal genes remain unknown. Analysis of a single data type is typically unsatisfactory in explaining complex traits that exhibit variation across multiple levels of biological regulation. To address these issues, we developed a computational framework called Camoco (Co-analysis of molecular components) that systematically integrates loci identified by GWAS with gene co-expression networks to identify a focused set of candidate loci with functional coherence. This framework analyzes the overlap between candidate loci generated from GWAS and the co-expression interactions that occur between them and addresses several biological considerations important for integrating diverse data types. On average, using this integrated approach, candidate gene lists identified by GWAS were reduced by two orders of magnitude. By incorporating co-expression network information, we can rapidly evaluate hundreds of GWAS experiments, producing focused sets of candidates with both strong associations with the phenotype of interest as well as evidence for functional coherence in the co-expression network. Identifying these candidates in a systematic and integrated manner is an important step toward resolving genes responsible for agriculturally important traits.