Common variants in CREB1 gene confer risk for bipolar disorder in Han Chinese

Recently, we have identified involvement of the gene encoding cAMP responsive element-binding 1 (CREB1) in risk of BD in European ancestry. CREB1 has significant genetic diversity between Europeans and Chinese, thereby resulting in diverged CREB1 genetic backgrounds. In this study, we aimed to determine whether CREB1 confers susceptibility to BD and cognitive dysfunction in Han Chinese. We recruited 572 patients with BD and 611 healthy controls for genetic study. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used for cognitive evaluation. SNP rs10932201 and rs3770704 within CREB1 were genotyped. The frequency of the G allele of rs10932201 was significantly greater in BD patients (41.8 %) than that in control subjects (37.2 %), with P = 0.02, corrected P = 0.04. There were significant differences in the scores of RBANS attention and total scores between the patients with different genotypes of rs10932201 polymorphism (P = 0.002 and 0.003, corrected P = 0.012 and 0.018, respectively). Post-hoc comparisons showed that rs10932201 G/G or G/A carriers had lower RBANS attention and total scores than those with A/A carriers (P = 0.002 and 0.004, P = 0.002 and 0.006, respectively). We observed a significant association between the rs10932201 and CREB1 expression in intralobular white matter (P = 0.037). Carriers with G allele have significantly lower levels of CREB1 expression in intralobular white matter than those without G allele. In conclusion, this study identified a novel BD risk SNP rs10932201 in Han Chinese and this SNP may be a risk factor for cognitive dysfunction in patients with BD.