| Sample Status |
The SCOPE BDsample is based on two independent case-control samples from Norway and Denmark, all included in the Scandinavian Collaboration on Psychiatric Etiology (SCOPE) study. The total number of subjects was 854 BD cases and 2,614 controls. The Norwegian patients (N=345) had been diagnosed with bipolar I disorder (N=230), bipolar II disorder (N=96), or BD not otherwise specified (N=19), according to DSM-IV using the Structural Clinical Interview for DSM-IV (SCID) [Spitzer et al., 1992]. The Danish sample (N=509) consisted of patients with bipolar affective disorder F31 (N=423) and manic episode F30 (N=3) according to ICD-10 (http://www.who.int/classifications/icd/en), bipolar I disorder according to DSM-IV (N=1), and BD (N=15), mania with psychosis (N=1), and bipolar with psychosis (N=66) according to the OPCRIT classification system. [McGuffin et al., 1991]. The SCOPE schizophrenia case-control sample. The SZ association studywas based on three independent case-control samples from Norway, Sweden and Denmark, included in the SCOPE. The Norwegian patients (N=349) had been diagnosed with SZ (N=272), schizoaffective disorder (N=59), schizophreniform disorder (N=15), and persistent delusional disorder (N=3) according to DSM-IV using the Structural Clinical Interview for DSM-IV (SCID) [Spitzer et al., 1992]. The Danish sample (N=467) consisted of patients with SZ (N=422), schizotypal personality disorder (N=4), persistent delusional disorder (N=2), and schizoaffective disorder (N=39) according to ICD-10 F20, F21, F22, and F25 using clinical interviews. The Swedish patients (N=257) had been diagnosed with SZ (N=224), schizoaffective disorder (N=25), or schizophreniform disorder (N=8), according to DSM-III-R/DSM-IV criteria using medical record reviews and clinical interviews. A total of 1,073 SZ cases and 2,919 control subjects were genotyped in this study. The Norwegian Scientific-Ethical Committees, the Norwegian Data Protection Agency, the Danish Scientific Committees, the Danish Data Protection Agency, the Ethical Committee of the Karolinska Hospital, the Stockholm Regional Ethical Committee, and the Swedish Data Inspection Board approved the study. All subjects have givenwritten informed consent prior to inclusion into the project. Icelandic bipolar disorder and schizophrenia case-control samples. The Icelandic BD and SZ samples consisted of 435 BD cases, 651 SZ cases, and 11,491 controls. Patients and controls were recruited from all over Iceland. For 316 of the BD patients, diagnoses were assigned according to Research Diagnostic Criteria (RDC) [Spitzer et al., 1978] through the use of the Schedule for Affective Disorders and Schizophrenia Lifetime Version (SADS-L) [Spitzer, 1977]. The remaining BD patients were recruited through a genetic study of anxiety and depression [Thorgeirsson et al., 2003] and had been characterized using the Composite International Diagnostic Interview (CIDI) [Peters and Andrews 1995; Wittchen et al., 1996]. For the Icelandic SZ patients, diagnoses were assigned according to RDC [Spitzer et al., 1978] through the use of the SADS-L [Spitzer, 1977. The 11,491 controls were recruited as a part of various genetic programs at deCODE genetics and were not screened for psychiatric disorders. |
| Result Summary |
Combining our Scandinavian samples with an Icelandic sample (N = 435 BD cases, 651 SZ cases, and 11,491 healthy controls), we found rs10994336 and rs9804190 to be nominally significantly associated with BD in this combined Nordic BD sample (N = 1,289/14,105). Nominal P was 0.015/0.018 (fixed/random effect) for rs10994336 (Bonferroni corrected P = 0.044/0.053) and 0.023 for rs9804190 (Bonferroni corrected P = 0.069). None of the SNPs were significantly associated with SZ in the combined Nordic SZ case-control sample (N = 1,724/14,410). These results further support that ANK3 is a susceptibility gene specific to BD and that more than one risk locus is involved. |