Study Report

Comment on Study

View All Comments on Study

Basic Info

Reference	Muller, D. J.,2011 PMID: 21443574
Citation	Muller, D. J., C. C. Zai, et al. (2011). "Association between the DAOA/G72 gene and bipolar disorder and meta-analyses in bipolar disorder and schizophrenia." Bipolar Disord 13(2): 198-207.
Disease Type	Bipolar Disorder & Schizophrenia
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	303 core BD families including 916 individuals
SNP/Region/Marker Size	5 SNPs
Predominant Ethnicity	Caucasian
Population	Canadian
Gender	The sample comprised 916 subjects,343 affected with BD (126 males and 217 females).
Age Group	Adults : Patients mean age was 35.6 years (SD = 11.2), with a mean age at onset of 20.1 years (SD = 7.61).

Detail Info

Sample Diagnosis	DSM
Sample Status	The families were recruited in Toronto and across central Canada through newspaper advertisements and hospital clinic referrals. The sample investigated was mostly recruited from outpatient populations and consisted of 303 nuclear families with at least one offspring (115 males and 188 females) who experienced at least one hypomanic or manic episode throughout life and had a DSM-IV diagnosis of bipolar I disorder (BDI), bipolar II disorder (BD-II), or schizoaffective disorder-bipolar type, based on a semistructured clinical interview [Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I)] and medical records . A total of 67 siblings (30 with BD) and 546 other first- or second-degree relatives (e.g., parents or grandparents; 10 with lifetime history of BD) were included. In total, the sample comprised 916 subjects: 343 affected with BD (126 males and 217 females) and 573 nonaffected relatives. The distribution of BD was as follows [per the DSM-IV, rapid cycling was defined as the occurrence of four or more (depressive and ? or manic) mood episodes within 12 months]: BD-I=215; BD-I with rapid cycling=7; BD-I with seasonal patterns=4; BD-I with mixed episodes = 3; BD-II= 70; BD-II with rapid cycling = 18; BD-II with seasonal patterns = 7; BD not otherwise specified = 3; schizoaffective disorder bipolar type = 16. Patients were mainly Caucasians of European origin (n = 308; 90%), with 6 Asians (1.7%), 2 African Americans (0.6%), and 27 (7.7%) of mixed or unknown ethnicities. Of the 303 BD probands, 157 displayed psychotic symptoms during their mood episodes (68 males and 89 females).
Technique	PCR and sequencing
Statistical Method	Analyses of single markers and haplotypes in DAOA ?G72 with BD were performed using the Family Based Association Test.
Result Summary	RESULTS: Marker rs1935062 was significantly associated with BD diagnosis in our sample (Z-score for C-allele= -2.33, p=0.02, uncorrected for genome-wide multiple comparisons). When we examined the subset of BD patients with psychotic symptoms (157 families), no significant results were obtained. Our meta-analysis yielded negative findings for DAOA/G72 markers in BD and positive findings for marker rs2391191 in SZ in East Asians. However, significant heterogeneity across studies limits interpretation. CONCLUSIONS: Our results provide evidence that suggests a possible role of the DAOA/G72 gene in BD and SZ. Marker rs1935062 may be specifically associated with BD, while marker rs2391191 may be associated with SZ but not with BD. Together with previous studies, these findings suggest that the DAOA/G72 gene confers susceptibility to both BD and SZ, but that different polymorphisms may potentially differentiate between these two disorders.

Genetic factors reported by this study for BD

SNPs reported by this study for BD (count: 5)

SNP	Related Gene(s)	Allele Change	Statistical Values	Author Comments	Result Category
rs947267	DAOA DAOA-AS1	G/T	FBAT: for total sample, variance of the S-statistic=69.8, Z-score=1.14, P-value = 0.25; for European sample, variance of the S-statistic=65.1, Z-score=1.49, P-value = 0.14; for BD patients with psychotic symptoms, variance of the S-statistic=34.8, Z-score=0.59, P-value = 0.55; for BD patients without psychotic symptoms, variance of the S-statistic=22.3, Z-score=0.95, P-value = 0.34	No significant association was observed. No significant association was observed.	Negative
rs2391191	DAOA DAOA-AS1	G/A	FBAT: for total sample, variance of the S-statistic=64.1, Z-score=1.39, P-value = 0.17; for European sample, variance of the S-statistic=59.9, Z-score=1.52, P-value = 0.13; for BD patients with psychotic symptoms, variance of the S-statistic=30, Z-score=0.55, P-value = 0.58; for BD patients without psychotic symptoms, variance of the S-statistic=21.5, Z-score=0.43, P-value = 0.67; Meta analysis: Fixed-effects model: ORA = 1.04, 95% confidence interval (CI): 0.97-1.11, p = 0.25; Random-effects model: ORA = 1.05, 95% CI: 0.97-1.12, p = 0.22.	No significant association was observed. No significant association was observed.	Negative
rs778294	DAOA DAOA-AS1	C/T	FBAT: for total sample, variance of the S-statistic=56.9, Z-score=-1.03, P-value = 0.3; for European sample, variance of the S-statistic=53.6, Z-score=-1, P-value = 0.32; for BD patients with psychotic symptoms, variance of the S-statistic=28.3, Z-score=-0.47, P-value = 0.64; for BD patients without psychotic symptoms, variance of the S-statistic=19, Z-score=-0.69, P-value = 0.49	No significant association was observed. No significant association was observed.	Negative
rs1341402	DAOA DAOA-AS1	T/C	FBAT: for total sample, variance of the S-statistic=47.1, Z-score=-0.63, P-value = 0.53; for European sample, variance of the S-statistic=45.6, Z-score=-0.49, P-value = 0.63; for BD patients with psychotic symptoms, variance of the S-statistic=24.3, Z-score=-0.31, P-value = 0.76; for BD patients without psychotic symptoms, variance of the S-statistic=15, Z-score=-0.52, P-value = 0.61	No significant association was observed. No significant association was observed.	Negative
rs1935062	DAOA DAOA-AS1	C/A	FBAT: for total sample, variance of the S-statistic=60.5, Z-score=-2.33, P-value = 0.02; for European sample, variance of the S-statistic=56.5, Z-score=-2.54, P-value = 0.01; for BD patients with psychotic symptoms, variance of the S-statistic=29, Z-score=-1.49, P-value = 0.14; for BD patients without psychotic symptoms, variance of the S-statistic=18.5, Z-score=-0.7, P-value = 0.49	Significant association was found in both BD total sample an...... Significant association was found in both BD total sample and BD European sample. More...	Positive

Haplotypes reported by this study for BD (count: 8)

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
rs2391191 - rs1935062 - rs947267	A-C-T	DAOA	FBAT:for total sample, variance of the S-statistic=48, Z-score=-2.67, P-value = 0.008, global P-value = 0.25; for European sample, variance of the S-statistic=44.7, Z-score=-3.13, P-value = 0.002, global P-value = 0.06	Significant association was found in individual P-value. Significant association was found in individual P-value.	Positive
rs2391191 - rs1935062 - rs947267 - rs778294	A-C-T-C	DAOA	FBAT:for total sample, variance of the S-statistic=48.1, Z-score=-2.67, P-value = 0.008, global P-value = 0.14; for European sample, variance of the S-statistic=44.9, Z-score=-3.13, P-value = 0.002, global P-value = 0.05	Significant association was found in individual P-value. Significant association was found in individual P-value.	Positive
rs1935062 - rs947267 - rs778294	C-T-C	DAOA	FBAT:for total sample, variance of the S-statistic=51.9, Z-score=-2.57, P-value = 0.01, global P-value = 0.03; for European sample, variance of the S-statistic=48.4, Z-score=-2.97, P-value = 0.003, global P-value = 0.02	Significant association was found in both individual P-value...... Significant association was found in both individual P-value and global P-value in BD. More...	Positive
rs2391191 - rs1935062	A-C	DAOA	FBAT:for total sample, variance of the S-statistic=53.1, Z-score=-2.37, P-value = 0.02, global P-value = 0.07; for European sample, variance of the S-statistic=49.9, Z-score=-2.8, P-value = 0.005, global P-value = 0.03	Significant association was found in individual P-value. Significant association was found in individual P-value.	Positive
rs1341402 - rs2391191 - rs1935062 - rs947267 - rs778294	T-A-C-T-C	DAOA	FBAT:for total sample, variance of the S-statistic=47.4, Z-score=-2.48, P-value = 0.01, global P-value = 0.42; for European sample, variance of the S-statistic=44.4, Z-score=-3, P-value = 0.003, global P-value = 0.24	Significant association was found in individual P-value. Significant association was found in individual P-value.	Positive
rs1935062 - rs947267	C-T	DAOA	FBAT:for total sample, variance of the S-statistic=51.8, Z-score=-2.56, P-value = 0.01, global P-value = 0.06; for European sample, variance of the S-statistic=48.3, Z-score=-2.93, P-value = 0.003, global P-value = 0.02	Significant association was found in individual P-value. Significant association was found in individual P-value.	Positive
rs1341402 - rs2391191 - rs1935062	T-A-C	DAOA	FBAT:for total sample, variance of the S-statistic=52.1, Z-score=-2.17, P-value = 0.03, global P-value = 0.23; for European sample, variance of the S-statistic=48.7, Z-score=-2.61, P-value = 0.009, global P-value = 0.11	Significant association was found in individual P-value. Significant association was found in individual P-value.	Positive
rs1341402 - rs2391191 - rs1935062 - rs947267	T-A-C-T	DAOA	FBAT:for total sample, variance of the S-statistic=47.3, Z-score=-2.46, P-value = 0.01, global P-value = 0.39; for European sample, variance of the S-statistic=44.3, Z-score=-2.99, P-value = 0.003, global P-value = 0.15	Significant association was found in individual P-value. Significant association was found in individual P-value.	Positive

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

Gene	Statistical Values/Author Comments	Result Category
DAOA	These findings suggest that the DAOA/G72 gene confers susceptibility to both BD and SZ, but that dif...... These findings suggest that the DAOA/G72 gene confers susceptibility to both BD and SZ, but that different polymorphisms may potentially differentiate between these two disorders. 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	rs2391191	DAOA DAOA-AS1	Meta analysis:Fixed-effects model:ORA = 1.03, 95% CI: 1.00-1.07, p = 0.07;Random-effects model: ORA = 1.05, 95% CI:0.97-1.13, p = 0.22.But in the East Asian subgroup (p = 0.02).	Significant association was observed in the East Asian subgroup.	Positive

Genes reported by this study for SZ/MDD

Disease	Gene	Description	Result Category
SZ	DAOA	These findings suggest that the DAOA/G72 gene confers susceptibility to both BD and SZ, but that different polymorphisms may potentially differentiate between these two disorders.	Positive