GLRB variants regulate nearby gene expression in human brain tissues

Qing-Jian Wu,Cheng-Jun Yan,Bao-Liang Sun,Shu-Yin Sun,Pi-Da Hao,Han-Xia Li,Ya-Jun Hou,Ming-Feng Yang,Chun-Jing Du

doi:10.1038/s41598-017-13702-8

Abstract

A recent genome-wide association study (GWAS) identified four genetic variants rs78726293, rs191260602, rs17035816 and rs7688285 in GLRB gene to be associated with panic disorder (PD) risk. In fact, GWAS is an important first step to investigate the genetics of human complex diseases. In order to translate into opportunities for new diagnostics and therapies, we must identify the genes perturbed by these four variants, and understand how these variant functionally contributes to the underlying disease pathogenesis. Here, we investigated the effect of these four genetic variants and the expression of three nearby genes including PDGFC, GLRB and GRIA2 in human brain tissues using the GTEx (version 6) and Braineac eQTLs datasets. In GTEx (version 6) dataset, the results showed that both rs17035816 and rs7688285 variants could significantly regulate PDGFC and GLRB gene expression. In Braineac dataset, the results showed that rs17035816 variant could significantly regulate GLRB and GRIA2 gene expression. We believe that these findings further provide important supplementary information about the regulating mechanisms of rs17035816 and rs7688285 variants in PD risk.

Highlights

Panic disorder (PD) is a kind of anxiety disorder, which is prevalent in a 2–3% life-time, and could cause a huge burden of disease[1]
We investigated the effect of these four genetic variants rs78726293, rs191260602, rs17035816 and rs7688285 and the expression of three nearby genes including PDGFC, GLRB and GRIA2 using two expression quantitative trait loci (eQTL) datasets
We focused on the two genetic variants including rs17035816 and rs7688285 and three genes including PDGFC, GLRB and GRIA2 in the following analysis

Summary

Introduction

Panic disorder (PD) is a kind of anxiety disorder, which is prevalent in a 2–3% life-time, and could cause a huge burden of disease[1]. Deckert et al recently performed a genome-wide association study of PD/agoraphobia (AG) using large-scale sample size[1] They successfully identified four genetic variants rs78726293, rs191260602, rs17035816 and rs7688285 in GLRB gene[1]. They further conducted an expression quantitative trait loci (eQTL) analysis to detect the functional effect of these four variants on the expression of GLRB and neighbor genes using the Genotype-Tissue Expression (GTEx) eQTL database[1] They evaluated the potential association between rs7688285 and GLRB mRNA expression levels using the post-mortem brain samples of 76 individuals[1]. The suggested association between these four genetic variants and gene expression of their nearby genes may have been adjusted by the genome wide FDR threshold, and may not be included in the online GTEx eQTL database. We investigated the effect of these four genetic variants rs78726293, rs191260602, rs17035816 and rs7688285 and the expression of three nearby genes including PDGFC, GLRB and GRIA2 using two eQTLs datasets

Methods

Results

Conclusion