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. Significantly, 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 high-expression allele is the risk allele for schizophrenia and bipolar disorder in the Han Chinese population.