1Institutes of Brain Science, Fudan University, Shanghai 200032, China
2School of Biological Sciences, Fudan University, Shanghai 200433, China
3Key Laboratory for Medical Neurobiology, Fudan University, Shanghai 200032, China
4Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Shanghai Ocean University, Ministry of Education, Shanghai 201306, China
5Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
Corresponding author: David Saffen. E-mail: saffen@fudan.edu.cn

Abstract 

22q11.2 deletion syndrome (DS) is a complex developmental disorder with a high incidence of psychiatric illnesses, including schizophrenia and mood disorders. Recent studies have identified Guanine Nucleotide Binding Protein (G protein) Beta Polypeptide 1-Like (GNB1L), located within the 1.5 Mbp 22q11.2 DS critical region, as a candidate liability gene for schizophrenia and bipolar disorder. In this study, we used mRNA expression measurements in Han Chinese postmortem temporal cortex and linkage disequilibrium (LD) analysis to show that GNB1L is regulated by a cis-acting genetic variant within the 3’-region of the gene. Signifi cantly, this variant is located within an LD block that contains all of the common SNPs previously shown to associate with schizophrenia and bipolar disorder in Han Chinese and Caucasian populations. Contrary to our expectations, re-analysis of previously published case-control study data in light of our mRNA expression results implies that the GNB1L highexpression allele is the risk allele for schizophrenia and bipolar disorder in the Han Chinese population.

Keywords

GNB1L; schizophrenia; linkage disequilibrium; eQTLs; cis-regulatory variants

[SpringerLink]