Study Report

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Basic Info

Reference	Oruc, L., 1997 (a) PMID: 9129719
Citation	Oruc, L., G. R. Verheyen, et al. (1997). "Analysis of the tyrosine hydroxylase and dopamine D4 receptor genes in a Croatian sample of bipolar I and unipolar patients." Am J Med Genet 74(2): 176-178.
Disease Type	Bipolar I Disorder & Major Depressive Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	42 unrelated patients with BP disorder, type I, 41 patients with UP recurrent major depression and 71 controls
SNP/Region/Marker Size	2 variants
Predominant Ethnicity
Population	Croatian
Gender	BPI: 25 females and 17 males; UPR: 33 females and 8 males; controls: 53 females and 18 males

Detail Info

Sample Diagnosis	Research Diagnostic Criteria (RDC)
Sample Status	The present study included 42 unrelated patients with BP disorder, type I; Forty-one unrelated patients were suffering from UP recurrent major depression; In our sample, 16 BPI and 10 UPR patients were positive for family history as defined by at least one first-degree relative suffering from major affective disorders. BPI: mean age at onset; 31.7, SD=5.7 years; UPR: age 30-74 years; mean age at onset, 39.6, SD=10.6 years
Technique	genotyping
Statistical Method	Exact tests for detecting deviations from Hardy-Weinberg equilibrium were performed using the Genepop version 2.0 software package [Raymond and Rousset, 1995]. The statistical significance of differences in specific allele and genotype frequencies, as well as homozygote/ heterozygote frequencies between patient and control populations, was calculated using Fisheros exact test (two-sided tests).
Result Summary	No significant association was found between bipolar disorder type I and unipolar recurrent major depression and the polymorphisms located near these genes. Therefore, the hypothesis that the tyrosine hydroxylase and the dopamine D4 receptor genes may be involved in the etiology of bipolar disorder and unipolar recurrent major depression is not supported in our study.

Genetic factors reported by this study for BD

Other variants reported by this study for BD (count: 2)

Variant Name	Related Gene	Type	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
DRD4 2-10 allele	DRD4	others			2 (218) Allele (bp): Fisherâ€™s exact test, P-value=1 for BPI, P-value=0.34 for BPI + UPR; 3 (266) Allele (bp): Fisherâ€™s exact test, P-value=1 for BPI, P-value=0.56 for BPI + UPR; 4 (314) Allele (bp): Fisherâ€™s exact test, P-value=1 for BPI, P-value=0.39 for BPI + UPR; 5 (362) Allele (bp): Fisherâ€™s exact test, P-value=1 for BPI, P-value=0.66 for BPI + UPR; 6 (410) Allele (bp): Fisherâ€™s exact test, P-value=0.74 for BPI, P-value=1 for BPI + UPR; 7 (458) Allele (bp): Fisherâ€™s exact test, P-value=0.55 for BPI, P-value=1 for BPI + UPR; 8 (506) Allele (bp): Fisherâ€™s exact test, P-value=0.28 for BPI, P-value=0.8 for BPI + UPR; 9 (554) Allele (bp): Fisherâ€™s exact test, P-value=0.48 for BPI, P-value=0.18 for BPI + UPR; 10 (602) Allele (bp): Fisherâ€™s exact test, P-value=0.74 for BPI, P-value=1 for BPI + UPR; Total: Fisherâ€™s exact test, P-value=0.38 for BPI, P-value=0.27 for BPI + UPR; Homozygotes: Fisherâ€™s exact test, P-value=1 for BPI, P-value=0.51 for BPI + UPR	No significant differences were observed at the single-allel...... No significant differences were observed at the single-allele level when comparing the UPR, BPI, or combined patient populations vs. controls. More...	Negative
TH 1-5 allele	TH	others			Fisherâ€™s exact test, P-value=0.76 for BPI, P-value=1 for BPI + UPR; Fisherâ€™s exact test, P-value=0.5 for BPI, P-value=0.26 for BPI + UPR; Fisherâ€™s exact test, P-value=0.38 for BPI, P-value=0.47 for BPI + UPR; Fisherâ€™s exact test, P-value=0.39 for BPI, P-value=0.72 for BPI + UPR; Fisherâ€™s exact test, P-value=0.88 for BPI, P-value=0.8 for BPI + UPR; Fisherâ€™s exact test, P-value=0.7 for BPI, P-value=0.72 for BPI + UPR; Fisherâ€™s exact test, P-value=0.08 for BPI, P-value=0.85 for BPI + UPR	For the TH polymorphism, the '1,2' genotype was more frequen...... For the TH polymorphism, the '1,2' genotype was more frequently observed among controls than in the patient group. However, this P value does not remain significant after applying a Bonferroni correction for multiple testing. When considering only BPI or UPR patients who were positive for family history, no significant differences were observed, either. More...	Negative

Genes reported by this study for BD (count: 2)

Gene	Statistical Values/Author Comments	Result Category
TH	Therefore, the hypothesis that the tyrosine hydroxylase and the dopamine D4 receptor genes may be in...... Therefore, the hypothesis that the tyrosine hydroxylase and the dopamine D4 receptor genes may be involved in the etiology of bipolar disorder and unipolar recurrent major depression is not supported in our study. More...	Negative
DRD4	Therefore, the hypothesis that the tyrosine hydroxylase and the dopamine D4 receptor genes may be in...... Therefore, the hypothesis that the tyrosine hydroxylase and the dopamine D4 receptor genes may be involved in the etiology of bipolar disorder and unipolar recurrent major depression is not supported in our study. More...	Negative

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

Other variants reported by this study for SZ/MDD

Disease	Variant Name	Related Gene	Type	Statistical Values	Description	Result Category
MDD	TH 1-5 allele	TH	others	Fisherâ€™s exact test, P-value=0.88 for UPR, P-value=1 for BPI + UPR; Fisherâ€™s exact test, P-value=0.32 for UPR, P-value=0.26 for BPI + UPR; Fisherâ€™s exact test, P-value=0.66 for UPR, P-value=0.47 for BPI + UPR; Fisherâ€™s exact test, P-value=1 for UPR, P-value=0.72 for BPI + UPR; Fisherâ€™s exact test, P-value=0.54 for UPR, P-value=0.8 for BPI + UPR; Fisherâ€™s exact test, P-value=0.79 for UPR, P-value=0.72 for BPI + UPR; Fisherâ€™s exact test, P-value=0.91 for UPR, P-value=0.85 for BPI + UPR	For the TH polymorphism, the '1,2' genotype was more frequently observed among controls than in the patient group. However, this P value does not remain significant after applying a Bonferroni correction for multiple testing. When considering only BPI or UPR patients who were positive for family history, no significant differences were observed, either.	Negative
MDD	DRD4 2-10 allele	DRD4	others	2 (218) Allele (bp): Fisherâ€™s exact test, P-value=0.18 for UPR, P-value=0.34 for BPI + UPR; 3 (266) Allele (bp): Fisherâ€™s exact test, P-value=0.49 for UPR, P-value=0.56 for BPI + UPR; 4 (314) Allele (bp): Fisherâ€™s exact test, P-value=0.19 for UPR, P-value=0.39 for BPI + UPR; 5 (362) Allele (bp): Fisherâ€™s exact test, P-value=1 for UPR, P-value=0.66 for BPI + UPR; 6 (410) Allele (bp): Fisherâ€™s exact test, P-value=1 for UPR, P-value=1 for BPI + UPR; 7 (458) Allele (bp): Fisherâ€™s exact test, P-value=0.71 for UPR, P-value=1 for BPI + UPR; 8 (506) Allele (bp): Fisherâ€™s exact test, P-value=0.8 for UPR, P-value=0.8 for BPI + UPR; 9 (554) Allele (bp): Fisherâ€™s exact test, P-value=0.44 for UPR, P-value=0.18 for BPI + UPR; 10 (602) Allele (bp): Fisherâ€™s exact test, P-value=1 for UPR, P-value=1 for BPI + UPR; Total: Fisherâ€™s exact test, P-value=0.26 for UPR, P-value=0.27 for BPI + UPR; Homozygotes: Fisherâ€™s exact test, P-value=0.24 for UPR, P-value=0.51 for BPI + UPR	No significant differences were observed at the single-allele level when comparing the UPR, BPI, or combined patient populations vs. controls.	Negative

Genes reported by this study for SZ/MDD

Disease	Gene	Description	Result Category
MDD	TH	Therefore, the hypothesis that the tyrosine hydroxylase and the dopamine D4 receptor genes may be involved in the etiology of bipolar disorder and unipolar recurrent major depression is not supported in our study.	Negative
MDD	DRD4	Therefore, the hypothesis that the tyrosine hydroxylase and the dopamine D4 receptor genes may be involved in the etiology of bipolar disorder and unipolar recurrent major depression is not supported in our study.	Negative