Association analysis of PALB2 and BRCA2 in bipolar disorder and schizophrenia in a scandinavian case-control sample

Martin Tesli; Lavinia Athanasiu; Morten Mattingsdal; Anna K Kähler; Omar Gustafsson; Bettina K Andreassen; Thomas Werge; Thomas Hansen; Ole Mors; Erling Mellerup; Pernille Koefoed; Erik G Jönsson; Ingrid Agartz; Ingrid Melle; Gunnar Morken; Srdjan Djurovic; Ole A Andreassen

doi:10.1002/ajmg.b.31098

Association analysis of PALB2 and BRCA2 in bipolar disorder and schizophrenia in a scandinavian case-control sample

Martin Tesli, Lavinia Athanasiu, Morten Mattingsdal, Anna K Kähler, Omar Gustafsson, Bettina K Andreassen, Thomas Werge, Thomas Hansen, Ole Mors, Erling Mellerup, Pernille Koefoed, Erik G Jönsson, Ingrid Agartz, Ingrid Melle, Gunnar Morken, Srdjan Djurovic, Ole A Andreassen

Department of Neuroscience

16 Citations (Scopus)

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). Wethen 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.

Original language	English
Journal	American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
Volume	153B
Issue number	7
Pages (from-to)	1276-82
Number of pages	7
ISSN	1552-4841
DOIs	https://doi.org/10.1002/ajmg.b.31098
Publication status	Published - Oct 2010

Keywords

BRCA2 Protein
Bipolar Disorder
Case-Control Studies
DNA Repair
Genetic Predisposition to Disease
Humans
Iceland
Neurogenesis
Nuclear Proteins
Polymorphism, Single Nucleotide
Scandinavia
Schizophrenia
Tumor Suppressor Proteins

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Tesli, M., Athanasiu, L., Mattingsdal, M., Kähler, A. K., Gustafsson, O., Andreassen, B. K., Werge, T., Hansen, T., Mors, O., Mellerup, E., Koefoed, P., Jönsson, E. G., Agartz, I., Melle, I., Morken, G., Djurovic, S., & Andreassen, O. A. (2010). Association analysis of PALB2 and BRCA2 in bipolar disorder and schizophrenia in a scandinavian case-control sample. American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, 153B(7), 1276-82. https://doi.org/10.1002/ajmg.b.31098

Association analysis of PALB2 and BRCA2 in bipolar disorder and schizophrenia in a scandinavian case-control sample. / Tesli, Martin; Athanasiu, Lavinia; Mattingsdal, Morten et al.
In: American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, Vol. 153B, No. 7, 10.2010, p. 1276-82.

Research output: Contribution to journal › Journal article › Research › peer-review

Tesli, M, Athanasiu, L, Mattingsdal, M, Kähler, AK, Gustafsson, O, Andreassen, BK, Werge, T, Hansen, T, Mors, O, Mellerup, E, Koefoed, P, Jönsson, EG, Agartz, I, Melle, I, Morken, G, Djurovic, S & Andreassen, OA 2010, 'Association analysis of PALB2 and BRCA2 in bipolar disorder and schizophrenia in a scandinavian case-control sample', American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, vol. 153B, no. 7, pp. 1276-82. https://doi.org/10.1002/ajmg.b.31098

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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). Wethen 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.",

keywords = "BRCA2 Protein, Bipolar Disorder, Case-Control Studies, DNA Repair, Genetic Predisposition to Disease, Humans, Iceland, Neurogenesis, Nuclear Proteins, Polymorphism, Single Nucleotide, Scandinavia, Schizophrenia, Tumor Suppressor Proteins",

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T1 - Association analysis of PALB2 and BRCA2 in bipolar disorder and schizophrenia in a scandinavian case-control sample

AU - Tesli, Martin

AU - Athanasiu, Lavinia

AU - Mattingsdal, Morten

AU - Kähler, Anna K

AU - Gustafsson, Omar

AU - Andreassen, Bettina K

AU - Werge, Thomas

AU - Hansen, Thomas

AU - Mors, Ole

AU - Mellerup, Erling

AU - Koefoed, Pernille

AU - Jönsson, Erik G

AU - Agartz, Ingrid

AU - Melle, Ingrid

AU - Morken, Gunnar

AU - Djurovic, Srdjan

AU - Andreassen, Ole A

PY - 2010/10

Y1 - 2010/10

N2 - 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). Wethen 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.

AB - 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). Wethen 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.

KW - BRCA2 Protein

KW - Bipolar Disorder

KW - Case-Control Studies

KW - DNA Repair

KW - Genetic Predisposition to Disease

KW - Humans

KW - Iceland

KW - Neurogenesis

KW - Nuclear Proteins

KW - Polymorphism, Single Nucleotide

KW - Scandinavia

KW - Schizophrenia

KW - Tumor Suppressor Proteins

U2 - 10.1002/ajmg.b.31098

DO - 10.1002/ajmg.b.31098

M3 - Journal article

C2 - 20872766

SN - 1552-4841

VL - 153B

SP - 1276

EP - 1282

JO - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics

IS - 7

ER -

Association analysis of PALB2 and BRCA2 in bipolar disorder and schizophrenia in a scandinavian case-control sample

Abstract

Keywords

UN SDGs

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