Association Analysis of PALB2 and BRCA2 in Bipolar Disorder and Schizophrenia in a Scandinavian Case-Control Sample

被引：18

作者：

Tesli, Martin ^{[1
,2
]}

Athanasiu, Lavinia ^{[1
,2
,3
]}

Mattingsdal, Morten ^{[3
]}

Kahler, Anna K. ^{[1
,2
,3
]}

Gustafsson, Omar ^{[2
]}

Andreassen, Bettina K. ^{[4
,5
]}

Werge, Thomas ^{[6
]}

Hansen, Thomas ^{[6
]}

Mors, Ole ^{[7
]}

Mellerup, Erling ^{[8
,9
]}

Koefoed, Pernille ^{[8
,9
]}

Jonsson, Erik G. ^{[12
]}

Agartz, Ingrid ^{[1
,12
,13
]}

Melle, Ingrid ^{[1
,2
]}

Morken, Gunnar ^{[10
,11
]}

Djurovic, Srdjan ^{[1
,2
,3
]}

Andreassen, Ole A. ^{[1
,2
]}

机构：

[1] Univ Oslo, Inst Psychiat, Oslo, Norway

[2] Oslo Univ Hosp, Dept Psychiat, N-0407 Oslo, Norway

[3] Oslo Univ Hosp, Dept Med Genet, N-0407 Oslo, Norway

[4] Univ Oslo, Dept Biostat, Oslo, Norway

[5] Univ Oslo, Dept Math, Oslo, Norway

[6] Copenhagen Univ Hosp, Res Inst Biol Psychiat, Mental Hlth Ctr Sct Hans, Roskilde, Denmark

[7] Aarhus Univ Hosp, Ctr Psychiat Res, DK-8000 Aarhus, Denmark

[8] Univ Copenhagen, Dept Neurosci & Pharmacol, Lab Neuropsychiat, Copenhagen, Denmark

[9] Ctr Psychiat, Dept Neurosci & Pharmacol, Copenhagen, Denmark

[10] St Olavs Hosp, Ostmarka Psychiat Dept, Trondheim, Norway

[11] Norwegian Univ Technol & Sci, Inst Neurosci, Trondheim, Norway

[12] Karolinska Inst & Hosp, Dept Clin Neurosci, HUBIN Project, Psychiat Sect, Stockholm, Sweden

[13] Diakonhjemmet Hosp, Dept Psychiat Res, Oslo, Norway

来源：

AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS | 2010年 / 153B卷 / 07期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

bipolar disorder; schizophrenia; PALB2; BRCA2; genetic association; WHOLE-GENOME ASSOCIATION; PROCEDURAL VALIDITY; RELIABILITY; RATIONALE; INTERVIEW; CRITERIA; ANXIETY;

D O I：

10.1002/ajmg.b.31098

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 x 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. (c) 2009 Wiley-Liss, Inc.

引用

页码：1276 / 1282

页数：7

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