Study Report

Basic Info

Reference	Pae, C. U., 2008 PMID: 17097106
Citation	Pae, C. U., H. S. Yu, et al. (2008). "Association of the trace amine associated receptor 6 (TAAR6) gene with schizophrenia and bipolar disorder in a Korean case control sample." J Psychiatr Res 42(1): 35-40.
Disease Type	Bipolar Disorder & Schizophrenia & Major Depressive Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	190 BD, 281 SZ, 187 MDD and 288 healthy controls
SNP/Region/Marker Size	5 SNPs
Predominant Ethnicity	Mongloid
Population	Korean
Gender	BD patients (87 males, 103 females), SZ patients (156 males, 125 females), MDD patients (55 males, 132 females), controls (134 males, 154 females)
Age Group	adults : BD patients: mean age=32.8 (SD=12.6) years; SZ patients: mean age=35.7 (SD=12.2) years; MDD patients: mean age=43.4 (SD=16.0) years; Controls: mean age=44.8 (SD=13.2) years

Detail Info

Sample Diagnosis	DSM-IV
Sample Status	SZ had an average age at onset=23.5 (SD=6.7) years; BD had an average age at onset=26.6 (SD=9.7) years; MDD had an average age at onset=41.3 (SD=15.8) years;
Technique	The high-throughput genotyping method of pyrosequencing
Statistical Method	Student t tests were used to test the significance of continuous variables. Pearson X² tests were used for categorical data. Data were analyzed using SPSS 13.0. Linkage disequilibrium between SNPs in the same gene was determined with Haploview V.3.12. Haploview was also used to detect significant departure from HWE (p < 0.05). Individual haplotype estimations from the population genotype data were obtained using the program, PHASE V 2.0
Result Summary	SNP rs6903874 was significantly associated with schizophrenia (p = 0.012) and bipolar disorder (p = 0.004). A three SNP haplotype consisting of alleles GCT from SNPs rs7452939, rs6903874 and rs6937506, respectively, was significantly over-represented in patients with schizophrenia (p = 0.0003) and bipolar disorder (p = 0.00002). A second three SNP haplotype (GTT) derived from the same SNPs was significantly under-represented in patients with bipolar disorder (p = 0.001). The GTT haplotype associations withstand the most rigorous corrections for multiple testing.

Genetic factors reported by this study for BD

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

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs8192625	TAAR6	T/C	C	Allele frequency (BID vs.control) 0.01 vs. 0.01; P-value > 0.05		Negative
rs6937506	TAAR6	C/T	T	Allele frequency (BID vs.control) 0.16 vs. 0.15; P-value > 0.05		Negative
rs6903874	TAAR6	T/C	C	Allele frequency (BID vs.control) 0.15 vs. 0.09; X²(df=1)= 8.08, P-value = 0.005	The minor allele (C) of SNP rs6903874 was significantly over...... The minor allele (C) of SNP rs6903874 was significantly over-represented among the patients with BID compared to controls. The significant association of rs6903874 with BID was not observed in the bipolar patients who manifested psychotic features, when analyzed alone vs. controls. More...	Positive
rs4305746	TAAR6	G/A	A	Allele frequency (BID vs.control) 0.40 vs. 0.45; P-value > 0.05		Negative

Haplotypes reported by this study for BD (count: 3)

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
rs7452939 - rs6903874 - rs6937506		TAAR6	Global X<sup>2</sup>=28.69, df=3, P-value = 0.00001	There were significant global differences in haplotype frequ...... There were significant global differences in haplotype frequency between BID patients compared to controls. More...	Positive
rs7452939 - rs6903874 - rs6937506	GTT	TAAR6	X<sup>2</sup>=11.46, df=1, P-value = 0.001	The GTT haplotype was significantly under-represented in pat...... The GTT haplotype was significantly under-represented in patients with BID compared to controls More...	Positive
rs7452939 - rs6903874 - rs6937506	GCT	TAAR6	X<sup>2</sup>=17.80, df=1, P-value = 0.00002	The GCT haplotype was significantly over-represented in the ...... The GCT haplotype was significantly over-represented in the patients with BID compared to controls. More...	Positive

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

Gene	Statistical Values/Author Comments	Result Category
TAAR6	SNP rs6903874 was significantly associated with schizophrenia (p = 0.012) and bipolar disorder (p = 0.004). A three SNP haplotype consisting of alleles GCT from SNPs rs7452939, rs6903874 and rs6937506, respectively, was significantly over-represented in patients with schizophrenia (p = 0.0003) and bipolar disorder (p = 0.00002). A second three SNP haplotype (GTT) derived from the same SNPs was significantly under-represented in patients with bipolar disorder (p = 0.001). The GTT haplotype associations withstand the most rigorous corrections for multiple testing.. These findings strongly support association of the TAAR6 gene with susceptibility to both schizophre...... These findings strongly support association of the TAAR6 gene with susceptibility to both schizophrenia and bipolar disorder in Korean patients. 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	rs8192625	TAAR6	Allele frequency (SZ vs.control) 0.02 vs. 0.01; P-value > 0.05		Negative
SZ	rs6937506	TAAR6	Allele frequency (SZ vs.control) 0.18 vs. 0.15; P-value > 0.05		Negative
SZ	rs6903874	TAAR6	Allele frequency (SZ vs.control) 0.14 vs. 0.09; X²(df=1)= 6.28, P-value = 0.012	The minor allele (C) of SNP rs6903874 was significantly over-represented among the patients with schizophrenia compared to controls.	Positive
SZ	rs4305746	TAAR6	Allele frequency (SZ vs.control) 0.38 vs. 0.45; X²(df=1)= 6.28, P-value = 0.019	The minor allele (A) of the adjoining SNP, rs7452939, was under-represented in the schizophrenia group, but this comparison did not survive Bonferroni correction.	Positive
MDD	rs6903874	TAAR6		The significant association of rs6903874 with BID was not observed in the overall groups of patients with MDD nor in the patients with psychotic MDD vs. controls.	Negative

Haplotypes reported by this study for SZ/MDD

Disease	Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Description	Result Category
SZ	rs7452939 - rs6903874 - rs6937506	GCT	TAAR6	X<sup>2</sup>=12.87, df=1, P-value = 0.0003	The GCT haplotype was significantly over-represented in the patients with schizophrenia compared to controls.	Positive
SZ	rs7452939 - rs6903874 - rs6937506		TAAR6	Global X<sup>2</sup>=18.49, df=3, P-value = 0.00042	There were significant global differences in haplotype frequency between schizophrenia patients compared to controls.	Positive
MDD	rs7452939 - rs6903874 - rs6937506		TAAR6	Global X<sup>2</sup>=8.80, df=3, P-value = 0.031	There were significant global differences in haplotype frequency between BID patients compared to controls.	Positive

Genes reported by this study for SZ/MDD

Disease	Gene	Description	Result Category
SZ	TAAR6	These findings strongly support association of the TAAR6 gene with susceptibility to both schizophrenia and bipolar disorder in Korean patients.	Positive