Zujia Wen1, Jianhua Chen2, Raja Amjad Waheed Khan1, Meng Wang1, Zhijian Song1, Zhiqiang Li1, Jiawei Shen1, Wenjin Li1, Yongyong Shi3. 1. Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education) and the Collaborative Innovation Center for Brain Science, Shanghai Jiao Tong University, Shanghai 200030, PR China. 2. Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education) and the Collaborative Innovation Center for Brain Science, Shanghai Jiao Tong University, Shanghai 200030, PR China; Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, PR China. 3. Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education) and the Collaborative Innovation Center for Brain Science, Shanghai Jiao Tong University, Shanghai 200030, PR China; Shanghai Changning Mental Health Center, 299 Xiehe Road, Shanghai 200042, PR China; Institute of Neuropsychiatric Science and Systems Biological Medicine, Shanghai Jiao Tong University, Shanghai 200042, PR China. Electronic address: shiyongyong@gmail.com.
Abstract
BACKGROUND: The NRGN gene locates on 11q24 and encodes a postsynaptic protein kinase substrate that binds calmodulin in the absence of calcium. In a previous genome-wide association study of schizophrenia in the Caucasian population, rs12807809 of NRGN was found to be significantly associated with schizophrenia, moreover, it was further found to be associated with bipolar disorder. METHODS: We recruited 1248 schizophrenia cases, 1344 bipolar disorder cases, 1056 major depressive disorder cases, and 1248 healthy controls from Han Chinese population. Rs12807809 and another two tag SNPs of NRGN were genotyped and analyzed in three diseases respectively. A meta-analysis of rs12807809 was also conducted to verify its association with schizophrenia in Han Chinese population. RESULTS: Rs7113041 was associated with bipolar disorder (odds ratio, 95% confidence interval (OR, 95% CI)=1.194, 1.032-1.383; Pgenotype=0.0126), and rs12278912 was associated with major depressive disorder (OR, 95% CI=0.789, 0.673-0.924; Pallele=0.0102, Pgenotype=0.0399) after Bonferroni correction. The "GA" haplotype of rs7113041-rs12278912 was significantly associated with schizophrenia, major depressive disorder and bipolar disorder (corresponding P values were 2.85E-04, 3.00E-03, and 5.40E-04 after Bonferroni correction). LIMITATIONS: Despite the association between NRGN and psychoses we have found, we failed to validate the positive variant rs12807809, which was reported in the Caucasian genome-wide association study both in our single site association test and the meta-analysis. Functional studies are needed to illuminate the role of NRGN in the pathogenesis of these mental disorders. CONCLUSIONS: Our findings prove that NRGN is a shared susceptibility gene of schizophrenia, major depression and bipolar disorder in Han Chinese, and this might provide a new target for the diagnosis and treatment of these mental disorders.
BACKGROUND: The NRGN gene locates on 11q24 and encodes a postsynaptic protein kinase substrate that binds calmodulin in the absence of calcium. In a previous genome-wide association study of schizophrenia in the Caucasian population, rs12807809 of NRGN was found to be significantly associated with schizophrenia, moreover, it was further found to be associated with bipolar disorder. METHODS: We recruited 1248 schizophrenia cases, 1344 bipolar disorder cases, 1056 major depressive disorder cases, and 1248 healthy controls from Han Chinese population. Rs12807809 and another two tag SNPs of NRGN were genotyped and analyzed in three diseases respectively. A meta-analysis of rs12807809 was also conducted to verify its association with schizophrenia in Han Chinese population. RESULTS:Rs7113041 was associated with bipolar disorder (odds ratio, 95% confidence interval (OR, 95% CI)=1.194, 1.032-1.383; Pgenotype=0.0126), and rs12278912 was associated with major depressive disorder (OR, 95% CI=0.789, 0.673-0.924; Pallele=0.0102, Pgenotype=0.0399) after Bonferroni correction. The "GA" haplotype of rs7113041-rs12278912 was significantly associated with schizophrenia, major depressive disorder and bipolar disorder (corresponding P values were 2.85E-04, 3.00E-03, and 5.40E-04 after Bonferroni correction). LIMITATIONS: Despite the association between NRGN and psychoses we have found, we failed to validate the positive variant rs12807809, which was reported in the Caucasian genome-wide association study both in our single site association test and the meta-analysis. Functional studies are needed to illuminate the role of NRGN in the pathogenesis of these mental disorders. CONCLUSIONS: Our findings prove that NRGN is a shared susceptibility gene of schizophrenia, major depression and bipolar disorder in Han Chinese, and this might provide a new target for the diagnosis and treatment of these mental disorders.