BackgroundBipolar disorder is a highly heritable polygenic disorder. Recentenrichment analyses suggest that there may be true risk variants forbipolar disorder in the expression quantitative trait loci (eQTL) in thebrain.AimsWe sought to assess the impact of eQTL variants on bipolar disorder riskby combining data from both bipolar disorder genome-wide associationstudies (GWAS) and brain eQTL.MethodTo detect single nucleotide polymorphisms (SNPs) that influenceexpression levels of genes associated with bipolar disorder, we jointlyanalysed data from a bipolar disorder GWAS (7481 cases and 9250 controls)and a genome-wide brain (cortical) eQTL (193 healthy controls) using aBayesian statistical method, with independent follow-up replications. Theidentified risk SNP was then further tested for association withhippocampal volume (n = 5775) and cognitive performance(n = 342) among healthy individuals.ResultsIntegrative analysis revealed a significant association between a braineQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayesfactor = 5.48; bipolar disorder P =5.85×10–5). Follow-up studies across multiple independentsamples confirmed the association of the risk SNP (rs6088662) with geneexpression and bipolar disorder susceptibility (P =3.54×10–8). Further exploratory analysis revealed thatrs6088662 is also associated with hippocampal volume and cognitiveperformance in healthy individuals.ConclusionsOur findings suggest that 20q11.22 is likely a risk region for bipolardisorder; they also highlight the informative value of integratingfunctional annotation of genetic variants for gene expression inadvancing our understanding of the biological basis underlying complexdisorders, such as bipolar disorder.