Genome wide identification of regulatory networks associated with general cognitive ability using a normalized alignment free similarity measure of promoter regions

TL;DR

This study introduces a normalized alignment free similarity measure, D2z, to identify potential regulatory networks from GWAS gene sets related to cognitive ability, revealing connections to mental retardation and neural development.

Contribution

The paper demonstrates the use of D2z for detecting regulatory relationships in gene sets with limited known regulatory elements, applied to GWAS data on cognitive ability.

Findings

Identified co-regulation networks among GWAS genes

Predicted additional genes linked to mental retardation

Found regulatory connection between GWAS genes and CHL1

Abstract

We show that a normalized alignment free similarity measure, called D2z, can be used to detect potential regulatory relations for gene sets when little is known about the regulatory elements involved. One scenario where such gene sets arise is genome wide association studies (GWAS). In this work we consider a gene set from a GWAS on childhood general cognitive ability. We build a co-regulation network for the GWAS genes based on the D2z scores, which shows potential co-regulatory relationships between the genes as well as predict additional genes that are likely to be part of the network. We found that the set of the predicted genes is enriched in genes associated with mental retardation and GO terms such as synapse and neuron development. In particular, we found strong evidence of regulatory connection between the GWAS genes and CHL1, a gene known to be involved in mental retardation.