Study Report

Reference	Meyer, J.,2005 PMID: 16098236
Citation	Meyer, J., K. Johannssen, et al. (2005). Rare variants of the gene encoding the potassium chloride co-transporter 3 are associated with bipolar disorder. Int J Neuropsychopharmacol 8(4): 495-504.
Disease Type	Bipolar Disorder & Schizophrenia
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	114 SZ patients,72 BD patients and 350 controls
SNP/Region/Marker Size	3 polymorphisms
Predominant Ethnicity	Caucasian
Population	German
Age Group	Adults : Mean age of patients was 46,SD=5 yr, of controls 32,SD=0.5 yr.

Sample Diagnosis	ICD
Sample Status	A total of 186 patients from the Lower Franconia area in Germany participated in the association study. These subjects were ascertained either at the Department of Psychiatry and Psychotherapy,University of Wuerzburg, or at the Psychiatric District Hospital Werneck. A total of 114 patients suffered from schizophrenia spectrum disorders according to ICD-10 criteria (31 paranoid type, 14 hebephrenic type, 4 catatonic type, 5 undifferentiated type, 23 residual type, 4 schizophrenia simplex, 1 schizotypical disorder, 9 delusional disorder, 23 schizoaffective disorder). All schizophrenia spectrum disorder patients were in-patients and had been seen by an experienced psychiatrist (A.R. and/or I.T.), and extensive semistructural interviews had been conducted along with chart reviews and, if possible, further information was retrieved from family informants and case records from other hospitals to ensure consistent diagnoses. Furthermore, one affected patient from each of the 12 families investigated in our genome scan (Sto¬ber et al.,2000, 2001) was genotyped. An additional sample of 72 in-patients suffering from bipolar disorder (66 patients) or severe depressive disorder with psychotic symptoms (six patients) according to ICD-10 criteria, were ascertained at the Department of Psychiatry, University of Wuerzburg. Bipolar patients had at least one manic and one depressive episode,and patients suffering from depression had at least two depressive episodes, and showed psychotic symptoms during these episodes. None of the subjects showed significant neurological comorbidity, epilepsy, mental retardation, or a history of substance abuse. A sample of DNA probes derived from of 350 control subjects has been collected by staff of the Departments of Psychiatry and Psychotherapy, and Transfusion Medicine of the University of Wuerzburg.The control sample consists of healthy blood donors from the same area as the patient group, which were not screened for a history of psychiatric disorders.
Technique	genotyping
Statistical Method	Single marker-disease associations were calculated by exact tests, X2 tests, and Armitage trend tests (Sasieni,1997) using the SAS statistical package SAS/STAT,version 8.1 (SAS Institute Inc., Cary, NC, USA). Haplotype analysis was performed with the program FastEH (Zhao et al., 2000; Zhao and Sham, 2002).
Result Summary	A case-control study was performed to assess association of variants with bipolar disorder and schizophrenia in a large sample. Several variants including two rare single nucleotide polymorphisms (G/A, G/A) in the promoter and 5'-UTR, and a thymidine insertion in intron 4 were found. The two G variants and the insertion variant were co-inherited with chromosome 15-related schizophrenia in a large family that strongly supports the region on chromosome 15q14-15 between markers D15S144 and D15S132. Furthermore, they are in linkage disequilibrium with each other, and significantly associated with bipolar disorder in a case-control study. Our data strongly suggest that rare variants of SLC12A6 may represent risk factors for bipolar disorder.