Study Report

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Basic Info

Reference	Scholz, C. J.,2010 PMID: 20052686
Citation	Scholz, C. J., C. P. Jacob, et al. (2010). "Functional variants of TSPAN8 are associated with bipolar disorder and schizophrenia." Am J Med Genet B Neuropsychiatr Genet 153B(4): 967-972.
Disease Type	Bipolar Disorder & Schizophrenia
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	269 SZ patients,169 bipolar patients and 362 controls
SNP/Region/Marker Size	15 SNPs
Predominant Ethnicity	Caucasian
Population	German

Detail Info

Sample Diagnosis	ICD-10
Sample Status	A total of 449 unrelated patients from the German Lower Franconia area, which were ascertained at the Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wurzburg, participated in this study. Two hundred sixty-nine patients suffered from SCZ according to ICD-10 criteria; all of them had chronic SCZ, as none of the subjects remitted completely. One hundred eighty suffered from BPD (thereof 9% bipolar-II;66%had apositive family history for affective disorders). A further 166 bipolar patients were ascertained at the Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark [Lundorf et al., 2005] and fulfilled the diagnostic criteria for research (ICD10-DCR) for BPD. These patients were all interviewed using a semi-structured interview. None of the subjects showed significant neurologic co-morbidity, epilepsy, mental retardation, or other somatic disorders suggesting organic psychosis. Patients with substance-induced disorders were excluded as well. The control sample consisted of 362 subjects,whowere healthy blood donors, staff members, or other healthy controls, all coming from the Lower Franconia region.
Technique	PCR and sequencing
Statistical Method	Cochran-Armitage test (dominant model)
Result Summary	Eight polymorphisms and four rare variants were identified. Of these, four polymorphisms at or in close proximity to exon d, g.83097C/T (HTR4-SVR (splice variant region) SNP1), g.83159G/A (HTR4-SVRSNP2), g.83164 (T)9-10 (HTR4-SVRSNP3), and g.83198A/G (HTR4-SVRSNP4), showed significant association with bipolar disorder with odds ratios of 1.5 to 2. These polymorphisms were in linkage disequilibrium, and only three common haplotypes were observed. One of the haplotypes showed significant association with bipolar disorder (P = 0.002). The genotypic and haplotypic associations with bipolar disorder were confirmed by transmission disequilibrium test in the NIMH Genetics Initiative Bipolar Pedigrees with ratios of transmitted to not transmitted alleles of 1.5 to 2.0 (P = 0.01). The same haplotype that showed association with bipolar disorder was suggested to be associated with schizophrenia in the case-control analysis (P = 0.003) but was not confirmed when Japanese schizophrenia families were tested. The polymorphisms associated with mood disorder were located within the region that encodes the divergent C-terminal tails of the 5-HT(4) receptor. These findings suggest that genomic variations in the HTR4 gene may confer susceptibility to mood disorder.

Genetic factors reported by this study for BD

SNPs reported by this study for BD (count: 14)

SNP	Related Gene(s)	Allele Change	Statistical Values	Author Comments	Result Category
rs4500567	TSPAN8	G/C	Cochran-Armitage test (dominant model): Bonferroni-Corrected P-value = 0.014	Significant association was found in BD. Significant association was found in BD.	Positive
rs3794217	TSPAN8	C/T	Cochran-Armitage test (dominant model): Bonferroni-Corrected P-value = 1	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs4760908	TSPAN8	C/A	Cochran-Armitage test (dominant model): Bonferroni-Corrected P-value = 1	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs11178655	TSPAN8	A/G	Cochran-Armitage test (dominant model): Bonferroni-Corrected P-value > 0.05	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs1397552	TSPAN8	A/G	Cochran-Armitage test (dominant model): Bonferroni-Corrected P-value = 1	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs1705233	TSPAN8	T/G	Cochran-Armitage test (dominant model): Bonferroni-Corrected P-value = 1	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs1796330	TSPAN8	G/C	Cochran-Armitage test (dominant model): Bonferroni-Corrected P-value = 1	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs1798086	TSPAN8	A/G	Cochran-Armitage test (dominant model): Bonferroni-Corrected P-value = 1	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs2270586	TSPAN8	T/C	Cochran-Armitage test (dominant model): Bonferroni-Corrected P-value = 1	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs3763978	TSPAN8	C/G	Cochran-Armitage test (dominant model): Bonferroni-Corrected P-value = 1	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs1705236	TSPAN8	T/A	Cochran-Armitage test (dominant model): Bonferroni-Corrected P-value = 1	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs17109370	TSPAN8	T/C	Cochran-Armitage test (dominant model): Bonferroni-Corrected P-value = 1	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs17226863	TSPAN8	C/G	Cochran-Armitage test (dominant model): Bonferroni-Corrected P-value = 1	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs17849952	TSPAN8	A/G	Cochran-Armitage test (dominant model): Bonferroni-Corrected P-value = 1	No significant association was observed in BD. No significant association was observed in BD.	Negative

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

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
rs1705236 - rs1798086 - rs17226863 - rs4500567 - rs1397552	A-A-G-C-G	TSPAN8	Association of Haplotypes:Nominal P-value = 0.15, Permutation P-value = 0.927	No significant association was found . No significant association was found .	Negative
rs1705236 - rs1798086 - rs17226863 - rs4500567 - rs1397552	A-G-C-C-G	TSPAN8	Association of Haplotypes:Nominal P-value = 0.519, Permutation P-value = 1	No significant association was found . No significant association was found .	Negative
rs1705236 - rs1798086 - rs17226863 - rs4500567 - rs1397552	A-G-G-C-G	TSPAN8	Association of Haplotypes:Nominal P-value = 0.482, Permutation P-value = 1	No significant association was found . No significant association was found .	Negative
rs1705236 - rs1798086 - rs17226863 - rs4500567 - rs1397552	A-G-G-G-G	TSPAN8	Association of Haplotypes:Nominal P-value = 0.001, Permutation P-value = 0.012	Significant association was found in BD. Significant association was found in BD.	Positive
rs1705236 - rs1798086 - rs17226863 - rs4500567 - rs1397552	T-G-G-C-A	TSPAN8	Association of Haplotypes:Nominal P-value = 0.587, Permutation P-value = 1	No significant association was found . No significant association was found .	Negative

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

Gene	Statistical Values/Author Comments	Result Category
TSPAN8	This suggests that TSPAN8 contributes to both diseases. This suggests that TSPAN8 contributes to both diseases.	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	rs4760908	TSPAN8	Cochran-Armitage test (dominant model):Bonferroni-Corrected P-value = 1	No significant association was observed.	Negative
SZ	rs4500567	TSPAN8	Cochran-Armitage test (dominant model):Bonferroni-Corrected P-value = 1	No significant association was observed.	Negative
SZ	rs2270586	TSPAN8	Cochran-Armitage test (dominant model):Bonferroni-Corrected P-value = 0.035	Significant association was found.	Positive
SZ	rs1798086	TSPAN8	Cochran-Armitage test (dominant model):Bonferroni-Corrected P-value = 1	No significant association was observed.	Negative
SZ	rs3794217	TSPAN8	Cochran-Armitage test (dominant model):Bonferroni-Corrected P-value = 1	No significant association was observed.	Negative
SZ	rs3763978	TSPAN8	Cochran-Armitage test (dominant model):Bonferroni-Corrected P-value = 0.031	Significant association was found.	Positive
SZ	rs17226863	TSPAN8	Cochran-Armitage test (dominant model):Bonferroni-Corrected P-value = 1	No significant association was observed.	Negative
SZ	rs17109370	TSPAN8	Cochran-Armitage test (dominant model):Bonferroni-Corrected P-value = 1	No significant association was observed.	Negative
SZ	rs1796330	TSPAN8	Cochran-Armitage test (dominant model):Bonferroni-Corrected P-value = 1	No significant association was observed.	Negative
SZ	rs17849952	TSPAN8	Cochran-Armitage test (dominant model):Bonferroni-Corrected P-value = 1	No significant association was observed.	Negative
SZ	rs1397552	TSPAN8	Cochran-Armitage test (dominant model):Bonferroni-Corrected P-value = 1	No significant association was observed.	Negative
SZ	rs11178655	TSPAN8	Cochran-Armitage test (dominant model):Bonferroni-Corrected P-value = 1	No significant association was observed.	Negative
SZ	rs1705236	TSPAN8	Cochran-Armitage test (dominant model):Bonferroni-Corrected P-value = 1	No significant association was observed.	Negative
SZ	rs1705233	TSPAN8	Cochran-Armitage test (dominant model):Bonferroni-Corrected P-value = 1	No significant association was observed.	Negative

Genes reported by this study for SZ/MDD

Disease	Gene	Description	Result Category
SZ	TSPAN8	This suggests that TSPAN8 contributes to both diseases.	Positive