Expression quantitative trait loci and genetic regulatory network analysis reveals that Gabra2 is involved in stress responses in the mouse

Abstract

Previous studies have revealed that the subunit α 2 (Gabra2) of the γ-aminobutyric acid receptor plays a critical role in the stress response. However, little is known about the gentetic regulatory network for Gabra2 and the stress response. We combined gene expression microarray analysis and quantitative trait loci (QTL) mapping to characterize the genetic regulatory network for Gabra2 expression in the hippocampus of BXD recombinant inbred (RI) mice. Our analysis found that the expression level of Gabra2 exhibited much variation in the hippocampus across the BXD RI strains and between the parental strains, C57BL/6J, and DBA/2J. Expression QTL (eQTL) mapping showed three microarray probe sets of Gabra2 to have highly significant linkage likelihood ratio statistic (LRS) scores. Gene co-regulatory network analysis showed that 10 genes, including Gria3, Chka, Drd3, Homer1, Grik2, Odz4, Prkag2, Grm5, Gabrb1, and Nlgn1 are directly or indirectly associated with stress responses. Eleven genes were implicated as Gabra2 downstream genes through mapping joint modulation. The genetical genomics approach demonstrates the importance and the potential power of the eQTL studies in identifying genetic regulatory networks that contribute to complex traits, such as stress responses.

Keywords::

• Anxiety
• expression QTL
• Gabra2
• genetical genomics
• genetic regulatory network
• hippocampus

Acknowledgements

This research was founded by National Natural Science Foundation of China (Nos 30771200, 30770666, and 30700517), key project of Jiangsu Natural Science Foundation (No. BK2007703) and Jiangsu Natural Science Foundation (No. BK2007065) and National Institute on Alcohol Abuse and Alcoholism (NIAAA) of USA (No. U01-AA014425). We thank David C. Airey for helpful comments on manuscript drafts.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.