BDgene

Core Gene from Gene Prioritization Pathways from PBA (Pathway-based Analysis) Enriched Pathways for Core Genes Enriched Pathways for Cross-disorder Genes

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Basic Info

Reference	Schulze, T. G.,2005 PMID: 16263850
Citation	Schulze, T. G., S. Ohlraun, et al. (2005). "Genotype-phenotype studies in bipolar disorder showing association between the DAOA/G30 locus and persecutory delusions: a first step toward a molecular genetic classification of psychiatric phenotypes." Am J Psychiatry 162(11): 2101-2108.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	300 BD patients and 300 controls in German group
SNP/Region/Marker Size	4 SNPs
Predominant Ethnicity	Caucasian
Population	German and Polish
Gender	Male/female:138/162 in BD patients and 121/179 in controls in German group,128/166 in BD patients and 155/196 in controls in Polish group
Age Group	Adults : Mean age(SD)(year):42.3(13.2) in BD patients and 47.1(15.2) in controls in German group,46.9(13.7) in BD patients and 43.7(9.5) in controls in Polish group

Detail Info

Sample Diagnosis	DSM
Sample Status	German group:This group comprised 300 patients with DSM-IV bipolar affective disorder (all bipolar type I) and 300 comparison subjects for whom we had genotype data available (3) (Table 1). Patients in this study were recruited from the same geographical area and were all of German descent. Patients were systematically recruited at the University of Bonn Department of Psychiatry. Subjects in the comparison group were anonymous blood donors of German descent recruited from the same geographical area as the patients. Written informed consent was obtained from all patients and comparison subjects. Of the 300 patients, 225 had been assessed by experienced psychiatrists with the Structured Clinical Interview for DSM-IV Disorders (SCID), and 75 patients had been assessed with the Schedule for Affective Disorders and Schizophrenia-Lifetime Version. Lifetime 'best estimate' diagnoses according to DSM-IV criteria were based on multiple sources of information including the structured interviews, medical records, and family history method. Consensus diagnoses were performed by two psychiatrists, and additional psychiatrists were included in the decision process whenever necessary. Furthermore, for the detailed polydiagnostic documentation of symptoms, we used the OPCRIT system. OPCRIT allows for the assessment and documentation of lifetime psychopathology without any preference for a particular classification system by decomposing diagnostic criteria into their component items. Replication study (Polish group). This group consisted of 294 bipolar affective disorder patients (type I: N=259, type II: N=35) and 311 comparison subjects from the Wielkopolska region (Western Poland). All individuals were of Polish descent. Patients were systematically recruited at two psychiatric hospitals, the Department of Psychiatry of the Poznan University of Medical Sciences and the psychiatric hospital in Koscian. The same diagnostic procedures were applied; all patients were interviewed with the SCID. Comparison subjects were drawn from anonymous blood donors, hospital staff, and medical students. Written informed consent was obtained from all patients and comparison subjects.
Replication Size	294 BD patients and 311 controls in Polish group
Technique	genotyping
Statistical Method	We performed both single-marker and haplotype analyses with the program COCAPHASE 2.40 (http://www.mrc-bsu.cam.ac.uk/personal/frank/software/unphased/). Using a standard unconditional logistic regression, this software package performs likelihood ratio tests under a log-linear model of the probability that an allele or a haplotype belongs to a case rather than a noncase; the expectation-maximization algorithm is used to resolve uncertain haplotypes and provide maximum-likelihood estimates of frequencies.
Result Summary	RESULTS: In a logistic regression, persecutory delusions were found to be the only significant explanatory variable for the DAOA/G30 risk genotype among 21 OPCRIT symptoms of psychosis. The authors therefore tested for association between DAOA/G30 and bipolar affective disorder in the 90 cases with a history of persecutory delusions. Whereas this subset showed strong association (odds ratio=1.83 for the best marker), the remaining larger sample of 165 patients with no such history did not differ from comparison subjects, suggesting that the association between DAOA/G30 and bipolar affective disorder is due to persecutory delusions. This was confirmed in an independent study of 294 bipolar affective disorder patients and 311 comparison subjects from Poland, in which an association between bipolar affective disorder and DAOA/G30 was only seen when case definition was restricted to cases with persecutory delusions. CONCLUSIONS: These data suggest that bipolar affective disorder with persecutory delusions constitutes a distinct subgroup of bipolar affective disorder that overlaps with schizophrenia.

SNPs reported by this study for BD (count: 4)

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs2391191	DAOA DAOA-AS1	G/A	G	For German group : All Patients With Bipolar Affective Disorder, P-value > 0.05 , OR=0.86, 95CI=0.91-1.47.Patients With a History of Psychotic Symptoms, P-value > 0.05 , OR=0.87, 95CI=0.66-1.15. Patients With No History of Psychotic Symptoms, P-value > 0.05 , OR=0.83, 95CI=0.58-1.19	No significant association was observed. No significant association was observed.	Negative
rs3918342	DAOA	T/C	C	For German group : All Patients With Bipolar Affective Disorder, P-value < 0.05 , OR=1.33, 95CI=1.06-1.68.Patients With a History of Psychotic Symptoms, P-value < 0.01 , OR=1.46, 95CI=1.12-1.91. Patients With No History of Psychotic Symptoms, P-value > 0.05 , OR=1.03, 95CI=0.73-1.46. For Polish group: All Patients With Bipolar Affective Disorder, P-value > 0.05 , OR=1.09, 95CI=0.86-1.39.Patients With a History of Psychotic Symptoms, P-value > 0.05 , OR=1.09, 95CI=0.79-1.49. Patients With No History of Psychotic Symptoms, P-value > 0.05 , OR=1.48, 95CI=0.96-2.28	Significant associations were found in German group. Significant associations were found in German group.	Positive
rs1341402	DAOA DAOA-AS1	G/A	G	For German group : All Patients With Bipolar Affective Disorder, P-value > 0.05 , OR=0.86, 95CI=0.91-1.47.Patients With a History of Psychotic Symptoms, P-value > 0.05 , OR=0.89, 95CI=0.68-1.19. Patients With No History of Psychotic Symptoms, P-value > 0.05 , OR=0.75, 95CI=0.52-1.08	No significant association was observed. No significant association was observed.	Negative
rs1421292	DAOA	A/T	T	For German group : All Patients With Bipolar Affective Disorder, P-value > 0.05 , OR=1.24, 95CI=0.98-1.56.Patients With a History of Psychotic Symptoms, P-value > 0.05 , OR=1.29, 95CI=0.98-1.69. Patients With No History of Psychotic Symptoms, P-value > 0.05 , OR=0.98, 95CI=0.69-1.40.For Polish group: All Patients With Bipolar Affective Disorder, P-value > 0.05 , OR=1, 95CI=0.80-1.27.Patients With a History of Psychotic Symptoms, P-value > 0.05 , OR=0.95, 95CI=0.70-1.28. Patients With No History of Psychotic Symptoms, P-value > 0.05 , OR=1.22, 95CI=0.81-1.86	No significant association was observed. No significant association was observed.	Negative

Haplotypes reported by this study for BD (count: 4)

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
rs1341402 - rs2391191 - rs3918342 - rs1421292	G-G-T-A	DAOA	For German group :All Patients With Bipolar Affective Disorder, P-value < 0.05 , OR=0.73	Significant association was found in global P-value. Significant association was found in global P-value.	Positive
rs1341402 - rs2391191 - rs3918342 - rs1421292	G-G-C-T	DAOA	For German group :All Patients With Bipolar Affective Disorder, P-value > 0.05 , OR=1.29	No significant association was found . No significant association was found .	Negative
rs3918342 - rs1421292	T-A	DAOA	For Polish group :All Patients With Bipolar Affective Disorder, P-value > 0.05 , OR=0.99	No significant association was found . No significant association was found .	Negative
rs3918342 - rs1421292	C-T	DAOA	For Polish group :All Patients With Bipolar Affective Disorder, P-value > 0.05 , OR=1.16	No significant association was found . No significant association was found .	Negative

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