Study Report

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Basic Info

Reference	Li, J.,2011(b) PMID: 21383261
Citation	Li, J., G. Zhou, et al. (2011). "Common variants in the BCL9 gene conferring risk of schizophrenia." Arch Gen Psychiatry 68(3): 232-240.
Disease Type	Bipolar Disorder & Schizophrenia & Major Depressive Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	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.
SNP/Region/Marker Size	10 SNPs
Predominant Ethnicity	Mongloid
Population	Chinese
Gender	Male/female:618/517 in BD patients ,570/464(stage 1),1041/977(stage 2) and 630/505(stage 3) in SZ patients,483/652 in MDD patients and 522/512(stage 1),1800/1803(stage 2) and 369/766(stage 3) in controls
Age Group	Adults : Mean age(SD)(year):36.6(13.8)[the onset age was 30.0(6.9)] in BD patients ,stage 1),38.8(14.1)[the onset age was 25.2(11.1)] for stage 1,42.7(16.1)[the onset age was 25.7(10.1)] for stage 2 and 35.4(7.2)[the onset age was 24.8(6.7)] for stage 3 in SZ patients, 35.1(11.6)[the onset age was 29.7( 6.9)] in MDD patients; 30.0 (8.7)for stage 1,61.5 (9.9) for stage 2 and 58.7(9.9) for stage 3 in controls

Detail Info

Sample Diagnosis	DSM
Sample Status	All participantswere recruited and interviewed by Shanghai Institute of Mental Health. All of our subjects in these studies were unrelated, living in Shanghai andwere of Shanghai origin. All cases were outpatients or stable in-patients. Eligible cases had to meet all of the following criteria namely that: (1) all cases were interviewed by two independent psychiatrists and were diagnosed strictly according to the Diagnostic and Statistical Manual for Mental Disorders-IV edition (DSM-IV) criteria; (2) all cases were diagnosed strictly according to Structured Clinical Interview for DSM-IV-TR Axis I Disorders- Patient Edition (SCID-I/P); (3) the age of all caseswas from18 to 65 years; (4) the psychiatric history of all cases must be at least two years; (5) all cases were excluded if they had other diseases, such as diabetes and hypertension; (6) all cases were excluded if they were biologically related to another study participant; and (7) approval was received for the study from the local Ethics Committee of Human Genetic Resources and all participants provided written informed consent in the study.
Technique	genotyping
Statistical Method	All calculations of allele and genotype frequencies, of the Hardy-Weinberg equilibrium, and of pairwise linkage disequilibrium were performed using the online SHEsis software(http://analysis.bio-x.cn).
Result Summary	RESULTS: During the first stage of our study, we found that rs672607 was significantly associated with schizophrenia (P = 2.69 x 10(-5)). During the second stage, rs672607 was successfully replicated (P = 1.33 x 10(-5)), and rs9326555 (P = .002), rs1240083 (P = 1.7 x 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 x 10(-5)), rs10494251 (P = .02), rs1240083 (P = 1.52 x 10(-4)), rs672607 (P = 1.23 x 10(-11)), rs688325 (P = 2.54 x 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.

Genetic factors reported by this study for BD

SNPs reported by this study for BD (count: 10)

SNP	Related Gene(s)	Allele Change	Statistical Values	Author Comments	Result Category
rs946903	BCL9 ACP6	C/T	Third-Stage Sample: for BPD, allele association P-value = 0.52, OR(95%CI)=0.96(0.83-1.10)	No significant association was observed. No significant association was observed.	Negative
rs9326555	BCL9	C/G	Third-Stage Sample: for BPD, allele association P-value = 0.13, OR(95%CI)=0.84(0.68-1.05)	No significant association was observed. No significant association was observed.	Negative
rs671056	BCL9	A/T	Third-Stage Sample: for BPD, allele association P-value = 0.46, OR(95%CI)=0.91(0.71-1.16)	No significant association was observed. No significant association was observed.	Negative
rs2236570	BCL9	A/G	Third-Stage Sample: for BPD, allele association P-value = 0.99, OR(95%CI)=1.00(0.88-1.14)	No significant association was observed. No significant association was observed.	Negative
rs3766512	BCL9 ACP6	C/T	Third-Stage Sample: for BPD, allele association P-value = 0.19, OR(95%CI)=1.08(0.96-1.22)	No significant association was observed. No significant association was observed.	Negative
rs1541187	BCL9	C/T	Third-Stage Sample: for BPD, allele association P-value = 0.09, OR(95%CI)=1.19(0.97-1.49)	No significant association was observed. No significant association was observed.	Negative
rs688325	BCL9	A/G	Third-Stage Sample: for BPD, allele association P-value = 0.14, OR(95%CI)=1.10(0.97-1.23)	No significant association was observed. No significant association was observed.	Negative
rs1240083	BCL9	A/G	Third-Stage Sample: for BPD, allele association P-value = 0.91, OR(95%CI)=0.99(0.85-1.16)	No significant association was observed. No significant association was observed.	Negative
rs672607	BCL9	A/G	Third-Stage Sample: for BPD, allele association P-value = 0.03, OR(95%CI)=0.86(0.75-0.99)	Significant association was found . Significant association was found .	Positive
rs10494251	BCL9	C/T	Third-Stage Sample: for BPD, allele association P-value = 0.32, OR(95%CI)=0.93(0.81-1.08)	No significant association was observed. No significant association was observed.	Negative

Genes reported by this study for BD (count: 1)

Gene	Statistical Values/Author Comments	Result Category
BCL9	These findings indicate that common variations in the BCL9 gene confer risk of schizophrenia and may...... 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. More...	Positive

Genetic factors reported by this study for SZ and/or MDD

SNPs reported by this study for SZ/MDD

Disease	SNP	Related Gene(s)	Statistical Values	Description	Result Category
SZ	rs10494251	BCL9	Third-Stage Sample:for SZ, allele association P-value = 0.53, OR(95%CI)=0.95(0.83-1.1);Combined Third-Stage Sample, allele association P-value = 0.02, OR(98%CI)=0.92(0.86-0.99)	Significant association was observed in SZ.	Positive
SZ	rs1541187	BCL9	Third-Stage Sample:for SZ, allele association P-value = 0.15, OR(95%CI)=1.16(0.95-1.43);Combined Third-Stage Sample, allele association P-value = 0.24, OR(98%CI)=1.06(0.97-1.17)	No significant association was observed.	Negative
SZ	rs1240083	BCL9	Third-Stage Sample:for SZ, allele association P-value = 0.09, OR(95%CI)=0.87(0.74-1.02);Combined Third-Stage Sample, allele association P-value = 0.000152, OR(98%CI)=0.86(0.79-0.93)	No significant association was observed.	Negative
SZ	rs3766512	BCL9 ACP6	Third-Stage Sample:for SZ, allele association P-value = 0.23, OR(95%CI)=1.08(0.95-1.22);Combined Third-Stage Sample, allele association P-value = 0.01, OR(98%CI)=1.08(1.02-1.15)	Significant association was observed in SZ.	Positive
SZ	rs2236570	BCL9	Third-Stage Sample:for SZ, allele association P-value = 0.7, OR(95%CI)=0.97(0.85-1.11);Combined Third-Stage Sample, allele association P-value = 0.88, OR(98%CI)=1.00(0.93-1.06)	No significant association was observed.	Negative
SZ	rs672607	BCL9	Third-Stage Sample:for SZ, allele association P-value = 0.006, OR(95%CI)=0.82(0.72-0.94);Combined Third-Stage Sample, allele association P-value = 0.0000000000123, OR(98%CI)=0.79(0.74-0.85)	Significant association was observed in SZ.	Positive
SZ	rs671056	BCL9	Third-Stage Sample:for SZ, allele association P-value = 0.63, OR(95%CI)=0.94(0.73-1.20);Combined Third-Stage Sample, allele association P-value = 0.48, OR(98%CI)=0.96(0.85-1.08)	No significant association was observed.	Negative
SZ	rs9326555	BCL9	Third-Stage Sample:for SZ, allele association P-value = 0.15, OR(95%CI)=1.16(0.94-1.43);Combined Third-Stage Sample, allele association P-value = 0.0000153, OR(98%CI)=1.27(1.14-1.41)	Significant association was observed in SZ.	Positive
SZ	rs688325	BCL9	Third-Stage Sample:for SZ, allele association P-value = 0.006, OR(95%CI)=1.19(1.05-1.33);Combined Third-Stage Sample, allele association P-value = 0.000254, OR(98%CI)=1.11(1.05-1.18)	Significant association was observed in SZ.	Positive
SZ	rs946903	BCL9 ACP6	Third-Stage Sample:for SZ, allele association P-value = 0.47, OR(95%CI)=0.95(0.83-1.10);Combined Third-Stage Sample, allele association P-value = 0.16, OR(98%CI)=0.95(0.89-1.02)	No significant association was observed.	Negative
MDD	rs10494251	BCL9	Third-Stage Sample:for MDD, allele association P-value = 0.04, OR(95%CI)=0.86(0.75-0.99)	Significant association was observed in MDD.	Positive
MDD	rs1541187	BCL9	Third-Stage Sample:for MDD, allele association P-value = 0.04, OR(95%CI)=1.23(1.01-1.52)	Significant association was observed in MDD.	Positive
MDD	rs1240083	BCL9	Third-Stage Sample:for MDD, allele association P-value = 0.63, OR(95%CI)=0.96(0.82-1.13)	No significant association was observed.	Negative
MDD	rs3766512	BCL9 ACP6	Third-Stage Sample:for MDD, allele association P-value = 0.13, OR(95%CI)=1.10(0.97-1.24)	No significant association was observed.	Negative
MDD	rs2236570	BCL9	Third-Stage Sample:for MDD, allele association P-value = 0.78, OR(95%CI)=1.02(0.89-1.16)	No significant association was observed.	Negative
MDD	rs672607	BCL9	Third-Stage Sample:for MDD, allele association P-value = 0.001, OR(95%CI)=0.79(0.69-0.90)	Significant association was observed in MDD.	Positive
MDD	rs671056	BCL9	Third-Stage Sample:for MDD, allele association P-value = 0.78, OR(95%CI)=1.03(0.81-1.03)	No significant association was observed.	Negative
MDD	rs9326555	BCL9	Third-Stage Sample:for MDD, allele association P-value = 0.99, OR(95%CI)=1.00(0.81-1.23)	No significant association was observed.	Negative
MDD	rs688325	BCL9	Third-Stage Sample:for MDD, allele association P-value = 0.02, OR(95%CI)=1.16(1.03-1.32)	Significant association was observed in MDD.	Positive
MDD	rs946903	BCL9 ACP6	Third-Stage Sample:for MDD, allele association P-value = 0.006, OR(95%CI)=0.82(0.71-0.95)	Significant association was observed in MDD.	Positive

Genes reported by this study for SZ/MDD

Disease	Gene	Description	Result Category
SZ	BCL9	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.	Positive
MDD	BCL9	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.	Positive