Study Report

Reference	Tesli, M.,2010 PMID: 20872766
Citation	Tesli, M., L. Athanasiu, et al. (2010). "Association analysis of PALB2 and BRCA2 in bipolar disorder and schizophrenia in a scandinavian case-control sample." Am J Med Genet B Neuropsychiatr Genet 153B(7): 1276-1282.
Disease Type	Bipolar Disorder & Schizophrenia
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	686 BD cases and 2,538 controls for BD study;781 SCZ cases and 2,839 controls for SCZ study
SNP/Region/Marker Size	2 SNPs
Predominant Ethnicity	Caucasian
Population	Scandinavian
Gender	Male/female:for BD cases,185/255 in Denmark sample,111/135 in Norway sample;for SCZ cases,210/153 in Denmark sample,90/76 in Norway sample and 156/96 in Sweden sample;for controls,1167/1040 in Denmark sample,158/172 in Norway sample and 187/114 in Sweden sample
Age Group	Adults : Mean age(SD)(year):for BD cases,53.1(14.0) in female and 49.4 (14.1) in male in Denmark sample,42.7 (13.2) in female and 42.4 (13.0) in male in Norway sample;for SCZ cases,48.7 (13.0) in female and 46.1(11.8) in male in Denmark sample,40.9(11.5) in female and 38.0 (9.7) in male in Norway sample and 60.3 (16.9) in female and 55.3 (14.0) in male in Sweden sample;for controls,46.1 (12.8) in female and 44.8 (11.6) in male in Denmark sample,39.2 (10.4) in female and 39.7 (10.4) in male in Norway sample and 54.0(10.5) in female and 53.0 (10.3) in male in Sweden sample

Sample Diagnosis	DSM and ICD-10
Sample Status	The bipolar disorder case-control sample. The BD sample is based on two independent case-control samples from Norway and Denmark, all included in the Scandinavian Collaboration of Psychiatric Etiology (SCOPE) study. The total number of subjects was 686 BD cases and 2,538 controls. The Norwegian patients (n=246) had been diagnosed with Bipolar I disorder (n=155), Bipolar II disorder (n=81) or Bipolar disorder NOS (n=10), according to DSM-IV using Structural Clinical Interview for DSM-IV (SCID) [Spitzer et al., 1992]. The Danish sample (n=440) consisted of patients with Bipolar affective disorder F31 (n=354) and Manic episode F30 (n=2) according to ICD-10, Bipolar I disorder according to DSM-IV (n=1), and Bipolar disorder (n=15), Mania with psychosis (n=1) and Bipolar with psychosis (n=66) according to the OPCRIT classification system [McGuffin et al., 1991].The schizophrenia case-control sample. The SCZ association study was based on three independent case-control samples from Norway, Sweden, and Denmark, included in the SCOPE. The Norwegian patients (n=166) had been diagnosedwith Schizophrenia (n=133), Schizoaffective disorder (n=26) and Schizophreniformdisorder (n=7) according to DSM-IV using Structural Clinical Interview for DSM-IV (SCID) [Spitzer et al., 1992]. The Danish sample (n=363) consisted of patients with Schizophrenia (n=333), Persistent delusional disorder (n=2) and Schizoaffective disorder (n=28) according to ICD-10 F20, F22, and F25 using clinical interviews. The Swedish patients (n=252) had been diagnosed with Schizophrenia (n=220), Schizoaffective disorder (n=24), or Schizophreniform disorder (n=8), according to DSM-III-R/DSM-IV criteria using record reviews and clinical interviews. The sample is described in more detail elsewhere [Hansen et al., 2007; Kahler et al., 2008]. A total of 781 SCZ cases and 2,839 controls subjects were successfully genotyped in this study.
Technique	genotyping(GoldenGate 1536plex assay and TaqMan SNP Genotyping Assay)
Statistical Method	Single SNP association tests were performed in PLINK, with the function model investigating best-fitting model and inheritance pattern. Correction was done for multiple testing with Bonferroni correction for all SNPs tested in each gene.
Result Summary	In a Scandinavian case-control sample (n = 686/2,538) we found the BRCA2 SNP rs9567552 to be significantly associated with BD (Nominal P = 0.00043). Additionally, we replicated the association between PALB2 SNP rs420259 and BD (Nominal P = 0.025). Neither the PALB2 SNP rs420259 nor the BRCA2 SNP rs9567552 were nominally significantly associated with the SCZ phenotype in our Scandinavian sample (n = 781/2,839). Our findings support PALB2 and BRCA2 as risk genes specifically for BD, and suggest that altered DNA repair related to neurogenesis may be involved in BD pathophysiology.