Context: Recent genome-wide association studies have revealed that common variations and rare copy-number variations contribute to the risk of mental disorders. Rare recurrent microdeletions at 1q21.1 were reported to be associated with schizophrenia, and the BCL9 gene at 1q21.1 was also a functional candidate gene for mental disorders.
Objectives: To investigate and validate whether common variations exist in a functional candidate gene in the copy-number variation region, and, if so, to determine whether these variations confer risk of schizophrenia or other mental disorders.
Design: A 3-stage case-control study.
Setting: Shanghai, China.
Participants: A total of 12 229 subjects were included: 5772 normal controls, 4187 patients with schizophrenia, 1135 patients with bipolar disorder patients, and 1135 patients with major depressive disorder. Main Outcome Measure During the first and second stages of our study, we genotyped 10 single-nucleotide polymorphisms using the ligation detection reaction method. During the third stage of our study, all single-nucleotide polymorphisms were genotyped using TaqMan technology (Applied Biosystems, Foster City, California).
Results: During the first stage of our study, we found that rs672607 was significantly associated with schizophrenia (P = 2.69 × 10(-5)). During the second stage, rs672607 was successfully replicated (P = 1.33 × 10(-5)), and rs9326555 (P = .002), rs1240083 (P = 1.7 × 10(-4)), and rs688325 (P = .006) were newly identified to be significant. During the third stage, we genotyped all single-nucleotide polymorphisms in 1135 patients with schizophrenia, 1135 patients with bipolar disorder, 1135 patients with major depressive disorder, and 1135 normal controls for further validation. Finally, when we combined all the data from the 3 stages of our schizophrenia study, we found that rs9326555 (P = 1.53 × 10(-5)), rs10494251 (P = .02), rs1240083 (P = 1.52 × 10(-4)), rs672607 (P = 1.23 × 10(-11)), rs688325 (P = 2.54 × 10(-4)), and rs3766512 (P = .01) were significant. Moreover, we found that rs672607 was significant in major depressive disorder (P = .001) and bipolar disorder (P = .03), and rs10494251 (P = .04), rs1541187 (P = .04), rs688325 (P = .02), and rs946903 (P = .006) were significant in major depressive disorder.
Conclusion: These findings indicate that common variations in the BCL9 gene confer risk of schizophrenia and may also be associated with bipolar disorder and major depressive disorder in the Chinese Han population.