title: Association analysis of PALB2 and BRCA2 in bipolar disorder and schizophrenia in a scandinavian case-control sample.
abstract: A recent genome-wide association study (GWAS) found significant association between the PALB2 SNP rs420259 and bipolar disorder (BD). The intracellular functions of the expressed proteins from the breast cancer risk genes PALB2 and BRCA2 are closely related. Therefore, we investigated the relation between genetic variants in PALB2 and BRCA2 and BD. Due to increasing evidence of genetic overlap between BD and schizophrenia (SCZ), we also investigated association with SCZ. 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). We then combined our sample with another Nordic case-control sample (n = 435/11,491) from Iceland, and added results from the Wellcome Trust Case Control Consortium (WTCCC) (n = 1,868/2,938) and the STEP-UCL/ED-DUB-STEP2 study (n = 2,558/3,274) in a meta-analysis which revealed a P-value of 1.2 × 10(-5) for association between PALB2 SNP rs420259 and BD (n = 5,547/20,241). 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. © 2010 Wiley-Liss, Inc.
authors.affiliation: Institute of Psychiatry, University of Oslo, Oslo, Norway. m.s.tesli@medisin.uio.no
authors.forename: Martin
authors.initials: M
authors.lastname: Tesli
authors.forename: Lavinia
authors.initials: L
authors.lastname: Athanasiu
authors.forename: Morten
authors.initials: M
authors.lastname: Mattingsdal
authors.forename: Anna K
authors.initials: AK
authors.lastname: Kähler
authors.forename: Omar
authors.initials: O
authors.lastname: Gustafsson
authors.forename: Bettina K
authors.initials: BK
authors.lastname: Andreassen
authors.forename: Thomas
authors.initials: T
authors.lastname: Werge
authors.forename: Thomas
authors.initials: T
authors.lastname: Hansen
authors.forename: Ole
authors.initials: O
authors.lastname: Mors
authors.forename: Erling
authors.initials: E
authors.lastname: Mellerup
authors.forename: Pernille
authors.initials: P
authors.lastname: Koefoed
authors.forename: Erik G
authors.initials: EG
authors.lastname: Jönsson
authors.forename: Ingrid
authors.initials: I
authors.lastname: Agartz
authors.forename: Ingrid
authors.initials: I
authors.lastname: Melle
authors.forename: Gunnar
authors.initials: G
authors.lastname: Morken
authors.forename: Srdjan
authors.initials: S
authors.lastname: Djurovic
authors.forename: Ole A
authors.initials: OA
authors.lastname: Andreassen
mesh_terms: D024682:BRCA2 Protein / Q000235:genetics*; D001714:Bipolar Disorder / Q000235:genetics*; D016022:Case-Control Studies; D004260:DNA Repair / Q000235:genetics; D000076164:Fanconi Anemia Complementation Group N Protein; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007055:Iceland; D055495:Neurogenesis / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012537:Scandinavian and Nordic Countries; D012559:Schizophrenia / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D024682:BRCA2 Protein; D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins