Study Report

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Basic Info

Reference	Saus, E.,2010 PMID: 20618448
Citation	Saus, E., V. Soria, et al. (2010). "A haplotype of glycogen synthase kinase 3beta is associated with early onset of unipolar major depression." Genes Brain Behav 9(7): 799-807.
Disease Type	Bipolar Disorder & Major Depressive Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	445 unrelated patients(256 MDD patients and 189 BD patients) and 440 control subjects
SNP/Region/Marker Size	11 SNPs
Predominant Ethnicity
Population	Spanish
Gender	female: 47.5% for controls,67.2% for MDD patients and 64% for BD patients
Age Group	Adults : Mean age(SD)(year):42.5(14.9) for controls,62.4(12.4),44.5 (14.7) at onset for MDD patients and 48.3(15.8),30.0 (12.7) at onset for BD patients

Detail Info

Sample Diagnosis	DSM
Sample Status	The study sample consisted of 445 unrelated patients and 440 control subjects. Sample recruitment has been described previously (Soria et al . 2010). Briefly, patients with a major depressive episode of at least moderate severity were consecutively recruited between 2004 and 2007 from the outpatient (41.3%) and inpatient (58.7%) sections of Psychiatry Department at the 'Hospital Universitari de Bellvitge' (female: 65.8%; mean age at recruitment: 56.4 years, SD 15.6; mean AAO of illness: 38.6 years, SD 15.5). The patients were diagnosed by experienced psychiatrists using the Structured Clinical Interview (SCID) (First et al . 1997) according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria (American Psychiatric Association 1994) for mood disorders (256 MDD, 189 BD). The baseline severity of the index depressive episode was assessed using the 21-item Hamilton Depression Rating Scale (HAM-D) (Hamilton 1960). The exclusion criteria were being under 18 years of age, presenting additional past or present psychiatric diagnoses other than MDD or BD, past or present history of psychoactive substance abuse except for nicotine and severe medical disease. Other sociodemographic and clinical variables such as AAO (defined as the age at which the patients first met DSM-IV criteria for either major depression or hypomania/mania), previous episodes and treatments were obtained by interviewing the patients and their nearest relatives in person and supported by available medical information. The control group consisted of 440 unrelated individuals (mean age: 42.5 years, SD 14.9) randomly selected from population registers in the same geographical area as the patients. Control subjects were screened for psychiatric diseases according to the 28- scaled Global Health Questionnaire (GHQ) (Lobo et al . 1986). Only unrelated subjects with no personal history of psychiatric disease, no clinically documented first-degree family history of psychiatric disease and a GHQ score <7 were included in the study.
Technique	genotyping
Statistical Method	Case-control association analyses to test for diagnosis phenotype (MDD and BD) were performed by logistic regression,while linear regression was used for quantitative traits (AAO and severity of depressive index episode).
Result Summary	RESULTS: Relative to the comparison subjects, subjects with bipolar disorder without panic disorder, but not those with comorbid bipolar disorder and panic disorder, showed significantly higher frequencies of the COMT Met158 and the short 5-HTTLPR alleles and genotypes. The differences in the frequencies of the TPH IVS7+218A alleles and genotypes approached statistical significance. CONCLUSIONS: The findings support the hypothesis that comorbid panic disorder identifies a genetic subtype of bipolar disorder and suggest a role for COMT and 5-HTT in vulnerability to these disorders.

Genetic factors reported by this study for BD

SNPs reported by this study for BD (count: 11)

SNP	Related Gene(s)	Allele Change	Statistical Values	Author Comments	Result Category
rs11925868	GSK3B	C/A	association analyses with diagnosis: codominant P-value = 0.069, dominant P-value = 0.063, recessive P-value = 0.405, additive P-value = 0.168	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs11921360	GSK3B	A/C	association analyses with diagnosis: codominant P-value = 0.696, dominant P-value = 0.56, recessive P-value = 0.687, additive P-value = 0.823	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs13314595	GSK3B	C/T	association analyses with diagnosis: codominant P-value = 0.274, dominant P-value = 0.578, recessive P-value = 0.198, additive P-value = 0.971	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs11927974	GSK3B	G/A	association analyses with diagnosis: codominant P-value = 0.437, dominant P-value = 0.81, recessive P-value = 0.234, additive P-value = 0.962	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs1054190	GSK3B NR1I2	C/T	association analyses with diagnosis: codominant P-value = 0.993, dominant P-value = 0.997, recessive P-value = 0.907, additive P-value = 0.973	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs9826659	GSK3B	A/G	association analyses with diagnosis: codominant P-value = 0.868, dominant P-value = 0.715, recessive P-value = 0.631, additive P-value = 0.623	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs7431209	GSK3B	G/A	association analyses with diagnosis: codominant P-value = 0.526, dominant P-value = 0.768, recessive P-value = 0.326, additive P-value = 0.87	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs334555	GSK3B	C/G	association analyses with diagnosis: codominant P-value = 0.446, dominant P-value = 0.204, recessive P-value = 0.714, additive P-value = 0.223	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs334538	RN7SL762P GSK3B	G/A	association analyses with diagnosis: codominant P-value = 0.587, dominant P-value = 0.5, recessive P-value = 0.35, additive P-value = 0.369	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs6438552	GSK3B	A/G	association analyses with diagnosis: codominant P-value = 0.339, dominant P-value = 0.219, recessive P-value = 0.702, additive P-value = 0.517	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs3732360	GSK3B NR1I2	T/C	association analyses with diagnosis: codominant P-value = 0.437, dominant P-value = 0.568, recessive P-value = 0.205, additive P-value = 0.336	No significant association was observed in BD. No significant association was observed in BD.	Negative

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

Gene	Statistical Values/Author Comments	Result Category
GSK3B	We could not find evidence for association to either MDD or BP, thus not replicating previous positi...... We could not find evidence for association to either MDD or BP, thus not replicating previous positive results from others with respect to BD diagnosis. More...	Negative

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
MDD	rs11921360	GSK3B	association analyses with diagnosis:codominant P-value = 0.097, dominant P-value = 0.038, recessive P-value = 0.223, additive P-value = 0.033, all P-value > 0.05 after multiple testing correction.	No significant association was observed.	Negative
MDD	rs1054190	GSK3B NR1I2	association analyses with diagnosis:codominant P-value = 0.521, dominant P-value = 0.393, recessive P-value = 0.547, additive P-value = 0.506	No significant association was observed.	Negative
MDD	rs9826659	GSK3B	association analyses with diagnosis:codominant P-value = 0.377, dominant P-value = 0.373, recessive P-value = 0.427, additive P-value = 0.693	No significant association was observed.	Negative
MDD	rs334555	GSK3B	association analyses with diagnosis:codominant P-value = 0.793, dominant P-value = 0.556, recessive P-value = 0.632, additive P-value = 0.506	No significant association was observed.	Negative
MDD	rs3732360	GSK3B NR1I2	association analyses with diagnosis:codominant P-value = 0.515, dominant P-value = 0.25, recessive P-value = 0.765, additive P-value = 0.302	No significant association was observed.	Negative
MDD	rs6438552	GSK3B	association analyses with diagnosis:codominant P-value = 0.228, dominant P-value = 0.277, recessive P-value = 0.109, additive P-value = 0.102	No significant association was observed.	Negative
MDD	rs7431209	GSK3B	association analyses with diagnosis:codominant P-value = 0.076, dominant P-value = 0.048, recessive P-value = 0.594, additive P-value = 0.159, all P-value > 0.05 after multiple testing correction.	No significant association was observed.	Negative
MDD	rs11925868	GSK3B	association analyses with diagnosis:codominant P-value = 0.811, dominant P-value = 0.572, recessive P-value = 0.845, additive P-value = 0.641	No significant association was observed.	Negative
MDD	rs11927974	GSK3B	association analyses with diagnosis:codominant P-value = 0.389, dominant P-value = 0.975, recessive P-value = 0.172, additive P-value = 0.909	No significant association was observed.	Negative
MDD	rs13314595	GSK3B	association analyses with diagnosis:codominant P-value = 0.899, dominant P-value = 0.923, recessive P-value = 0.68, additive P-value = 0.947	No significant association was observed.	Negative
MDD	rs334538	RN7SL762P GSK3B	association analyses with diagnosis:codominant P-value = 0.992, dominant P-value = 0.907, recessive P-value = 0.946, additive P-value = 0.902	No significant association was observed.	Negative

Genes reported by this study for SZ/MDD

Disease	Gene	Description	Result Category
MDD	GSK3B	We could not find evidence for association to either MDD or BP.	Negative