вход по аккаунту


Association analysis of PALB2 and BRCA2 in bipolar disorder and schizophrenia in a scandinavian caseЦcontrol sample.

код для вставкиСкачать
Neuropsychiatric Genetics
Association Analysis of PALB2 and BRCA2 in Bipolar
Disorder and Schizophrenia in a Scandinavian
Case–Control Sample
Martin Tesli,1,2* Lavinia Athanasiu,1,2,3 Morten Mattingsdal,3 Anna K. K€ahler,1,2,3 Omar Gustafsson,2
Bettina K. Andreassen,4,5 Thomas Werge,6 Thomas Hansen,6 Ole Mors,7 Erling Mellerup,8,9
Pernille Koefoed,8,9 Erik G. J€onsson,12 Ingrid Agartz,1,12,13 Ingrid Melle,1,2 Gunnar Morken,10,11
Srdjan Djurovic,1,2,3 and Ole A. Andreassen1,2
Institute of Psychiatry, University of Oslo, Oslo, Norway
Department of Psychiatry, Oslo University Hospital, Ulleval, Oslo, Norway
Department of Medical Genetics, Oslo University Hospital, Ulleval, Oslo, Norway
Department of Biostatistics, University of Oslo, Oslo, Norway
Department of Mathematics, University of Oslo, Oslo, Norway
Research Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Copenhagen University Hospital, Roskilde, Denmark
Center for Psychiatric Research, Aarhus University Hospital, Aarhus, Denmark
Department of Neuroscience and Pharmacology, Laboratory of Neuropsychiatry, University of Copenhagen, Copenhagen, Denmark
Department of Neuroscience and Pharmacology, Center of Psychiatry, Copenhagen, Denmark
Østmarka Psychiatric Department, St. Olavs Hospital, Trondheim, Norway
Institute of Neuroscience, Norwegian University of Technology and Science, Trondheim, Norway
Department of Clinical Neuroscience, HUBIN Project, Psychiatry Section, Karolinska Institutet and Hospital, Stockholm, Sweden
Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway
Received 19 January 2010; Accepted 9 April 2010
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 ¼ 686/2,538) we found the
BRCA2 SNP rs9567552 to be significantly associated with BD
(Nominal P ¼ 0.00043). Additionally, we replicated the association between PALB2 SNP rs420259 and BD (Nominal P ¼ 0.025).
We then combined our sample with another Nordic case–control
How to Cite this Article:
Tesli M, Athanasiu L, Mattingsdal M, K€ahler
AK, Gustafsson O, Andreassen BK, Werge T,
Hansen T, Mors O, Mellerup E, Koefoed P,
onsson 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.
Am J Med Genet Part B 153B:1276–1282.
Additional Supporting Information may be found in the online version of this article.
Grant sponsor: University of Oslo; Grant sponsor: Research Council of Norway; Grant Numbers: 167153/V50, 163070/V50; Grant sponsor: SouthEast
Norway Health Authority; Grant Number: 2004123; Grant sponsor: Danish National Psychiatric Research Foundation; Grant sponsor: Lundbeck
Foundation; Grant sponsor: Stanley Medical Research Institute; Grant sponsor: Wallenberg Foundation; Grant sponsor: HUBIN Project; Grant sponsor:
Swedish Medical Research Council; Grant Numbers: 2006-2992, 2006-986, 2008-2167.
*Correspondence to:
Martin Tesli, M.D., Section for Psychosis Research, Division of Psychiatry, Department for Research and Development, Oslo University Hospital, Building
49, Ulleval, Kirkeveien 166, N-0407 Oslo, Norway. E-mail:
Published online 24 May 2010 in Wiley Online Library (
DOI 10.1002/ajmg.b.31098
Ó 2010 Wiley-Liss, Inc.
sample (n ¼ 435/11,491) from Iceland, and added results from
the Wellcome Trust Case Control Consortium (WTCCC)
(n ¼ 1,868/2,938) and the STEP-UCL/ED-DUB-STEP2 study
(n ¼ 2,558/3,274) in a meta-analysis which revealed a P-value of
1.2 105 for association between PALB2 SNP rs420259 and BD
(n ¼ 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 ¼ 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.
Ó 2009 Wiley-Liss, Inc.
[WTCCC, 2007], was associated with BD in a Scandinavian sample
of 686 BD cases and 2,538 controls, from now on called ‘‘Total
SCOPE BD sample.’’ We also genotyped 10 BRCA2 tagSNPs
selected by using the HapMap in a smaller but overlapping BD
sample comprising 554 cases and 1,419 controls, from now on
called ‘‘SCOPE BD Subsample.’’ The most significant BRCA2 SNPs
from this subsample was genotyped in the remaining subjects of the
Total SCOPE BD sample. In the second phase of our study, we
investigated if the PALB2 SNP rs420259 and the nominally significant BRCA2 tagSNPs from the SCOPE BD Subsample were associated with SCZ in the SCOPE SCZ sample of 781 cases and 2,839
Key words: bipolar disorder; schizophrenia; PALB2; BRCA2;
genetic association
Sample Description
Bipolar disorder (BD) and schizophrenia (SCZ) are severe mental
disorders with high heritability, but the underlying molecular
genetic mechanisms are still not well understood [Keshavan
et al., 2008; Newberg et al., 2008]. Epidemiological as well as
molecular genetic studies are consistent with a polygenic model
[Craddock et al., 1995; Owen et al., 2009], in which many genetic
variants must interact with each other and with environmental
factors to give rise to BD and SCZ. Furthermore, results from recent
epidemiological and association studies indicate a genetic overlap
between these two disorders [Lichtenstein et al., 2009; Moskvina
et al., 2009].
A recent genome-wide association study (GWAS) found a
significant association between BD and the single nucleotide polymorphism (SNP) rs420259 in PALB2 (partner and localizer of
BRCA2) (Genotypic P-value ¼ 6.3 108) [WTCCC, 2007].
PALB2 is located on chromosome 16 and encodes for the protein
PALB2, which co-localizes with BRCA2 (breast cancer 2, early
onset) in the cell nucleus and promotes its localization and stability
in cellular structures like chromatin and nuclear matrix [Xia et al.,
2006]. BRCA2 is located on chromosome 13 and encodes for the
protein BRCA2, which is involved in DNA repair. A dysfunction in
BRCA2 leads to an increased risk of developing certain forms of
cancer [Tutt and Ashworth, 2002], and recent evidence suggests
that mutations in PALB2 itself also increases the risk for breast
cancer [Rahman et al., 2007]. Interestingly, a recent study showed
that BRCA2 is required for normal neurogenesis in mice [Frappart
et al., 2007]. Thus, it is possible that alterations in these two
functionally related genes may lead to abnormal neurogenesis in
humans, which in turn might give rise to severe psychiatric
In this study we investigated the association between PALB2 and
BRCA2 and severe psychiatric disorders, as well as the potential
genetic overlap between BD and SCZ. For that purpose we genotyped PALB2 and BRCA2 SNPs in Scandinavian BD and SCZ
case–control samples.
In the first phase of our study, we investigated if the PALB2 SNP
rs420259 which was highly associated with BD in the WTCCC study
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 ¼ 246)
had been diagnosed with Bipolar I disorder (n ¼ 155), Bipolar II
disorder (n ¼ 81) or Bipolar disorder NOS (n ¼ 10), according to
DSM-IV using Structural Clinical Interview for DSM-IV (SCID)
[Spitzer et al., 1992]. The Danish sample (n ¼ 440) consisted of
patients with Bipolar affective disorder F31 (n ¼ 354) and Manic
episode F30 (n ¼ 2) according to ICD-10, Bipolar I disorder
according to DSM-IV (n ¼ 1), and Bipolar disorder (n ¼ 15),
Mania with psychosis (n ¼ 1) and Bipolar with psychosis
(n ¼ 66) according to the OPCRIT classification system
[McGuffin et al., 1991].
The BD, SCZ, and control samples are further described in
Table I.
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 ¼ 166) had been diagnosed with Schizophrenia (n ¼ 133), Schizoaffective disorder (n ¼ 26) and Schizophreniform disorder (n ¼ 7) according to DSM-IV using Structural
Clinical Interview for DSM-IV (SCID) [Spitzer et al., 1992].
The Danish sample (n ¼ 363) consisted of patients with
Schizophrenia (n ¼ 333), Persistent delusional disorder (n ¼ 2)
and Schizoaffective disorder (n ¼ 28) according to ICD-10 F20,
F22, and F25 using clinical interviews. The Swedish patients
(n ¼ 252) had been diagnosed with Schizophrenia (n ¼ 220),
Schizoaffective disorder (n ¼ 24), or Schizophreniform disorder
(n ¼ 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.
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 given written informed consent prior to inclusion into
the project.
TABLE I. Sample Characterization
Mean age (SD)a
Mean age (SD)a
Mean age (SD)a
53.1 (14.0)
49.4 (14.1)
48.7 (13.0)
46.1 (11.8)
46.1 (12.8)
44.8 (11.6)
42.7 (13.2)
42.4 (13.0)
40.9 (11.5)
38.0 (9.7)
39.2 (10.4)
39.7 (10.4)
60.3 (16.9)
55.3 (14.0)
54.0 (10.5)
53.0 (10.3)
BD, bipolar disorder; SCZ, schizophrenia; SD, standard deviation.aMean age in 2009.
Replication Samples
Icelandic bipolar disorder case–control sample. The Icelandic
BD sample consisted of 435 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 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]. The 11,491 controls were recruited as a part of various
genetic programs at deCODE genetics and were not screened for
psychiatric disorders.
WTCCC bipolar disorder case–control sample. The WTCCC
BD sample consisted of 1,868 cases and 2,938 controls, all from a
British population [WTCCC, 2007].
STEP-UCL/ED-DUB-STEP2 bipolar disorder case–control
sample. The STEP-UCL/ED-DUB-STEP2 BD sample (n ¼
2,558/3,274) consisted of the STEP-UCL BD sample (n ¼ 1,460/
2,007) and the ED-DUB-STEP2 BD sample (n ¼ 1,098/1,267), and
is better described elsewhere [Ferreira et al., 2008; Sklar et al., 2008].
SNP Selection and Genotyping
To cover most of the common variants in BRCA2 in the SCOPE BD
Subsample with tagSNPs, we used a structured gene-wide
approach, based on the HapMap CEU population. TagSNP selection was performed at the HapMap website using pair-wise tagging,
with r2 0.8 [de Bakker et al., 2005] (; HapMap
Data Rel 22/phaseII Apr07) and minor allele frequency
(MAF) 0.05. The actual tagging efficiency of successfully genotyped tagSNPs was calculated at the Tagger website (www.broad.
Genomic DNA was extracted from whole blood. Ten BRCA2
tagSNPs were genotyped in the SCOPE BD Subsample using the
GoldenGate 1536plex assay (Illumina, Inc., San Diego, CA) on
Illumina BeadStation 500GX at the SNP Technology Platform,
Uppsala University, Sweden (, accredited by
the Swedish accreditation agency SWEDAC, and approved according to a quality system based on the international SS-EN ISO/IEC
17025 standard.
For the rest of the genotyping in this study we used the TaqMan
SNP Genotyping Assay (Applied Biosystems, Foster City, CA), predesigned assays, according to manufacturer’s instructions. Allelic
discrimination of samples was done using an ABI PRISM 7900HT
Sequence Detection System (Applied Biosystems) in combination
with the SDS 3.2 software. In each experiment, a minimum of four
‘‘no template Controls’’ (NTC) were also used. None of these NTCs
showed any signal in the experiments performed.
Statistical Analysis
SCOPE bipolar disorder and schizophrenia case–control samples. All SNPs were tested for deviation from Hardy–Weinberg
equilibrium (HWE) in the controls using PLINK (version 1.04; [Purcell et al., 2007].
SNPs with P < 0.01 in controls were considered in Hardy–
Weinberg disequilibrium (HWD) and excluded.
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.
Although a recent report found no population stratification
between our three Scandinavian SCZ subsamples [Kahler et al.,
2008], potential differences in allele frequencies between the cases
and controls were investigated with the Cochran–Mantel–Haenzsel
(CMH) test, using the population as stratification factor. The
heterogeneity of the population-based odds ratios (ORs) of the
different populations was evaluated with the Breslow–Day test.
Pairwise SNP SNP interaction analysis was performed for the
PALB2 SNP rs420259 and the most significant BRCA2 tagSNPs. All
these tests were undertaken in PLINK.
Meta-analysis. Association tests between BD and the PALB2
SNP rs420259 in the SCOPE/Icelandic/WTCCC BD sample
(n ¼ 2,989/16,967) were performed in PLINK. To evaluate
and correct for population stratification, the CMH and the
The main findings of the present study were a replication of the
association between the PALB2 SNP rs420259 and BD from the
1.04 (0.91–1.20)
1.05 (0.91–1.20)
0.84 (0.72–0.98)
1.32 (1.13–1.54)
0.00043 (0.0043)
Breslow–Day test
OR (95% CI)
CMH test
P (Bonferroni
CI, confidence interval; CMH, Cochran–Mantel–Haenszel; OR, odds ratio.
SNP (gene)
Total BD sample
rs420259 (PALB2)
rs9567552 (BRCA2)
Total SCZ sample
rs420259 (PALB2)
rs9567552 (BRCA2)
All P-values presented here are based on the CMH test. More
detailed results are presented in Tables II and III and Table I in
Supplementary Material.
SCOPE bipolar disorder case–control sample. As seen in
Table II, P-value for association between PALB2 SNP rs420259
and BD was 0.025. OR for the minor allele G was 0.84, A was risk
Two of 10 BRCA2 tagSNPs showed nominal significant association with BD in the SCOPE BD Subsample (P ¼ 0.00037 for
rs9567552 and P ¼ 0.027 for rs2320236), but only rs9567552 survived Bonferroni correction (P ¼ 0.0037) (Table I Supplementary
material). rs9567552 attained a P-value of 0.00043 in the Total
SCOPE BD sample (P ¼ 0.0043 after Bonferroni correction)
(Table II). OR for minor allele T was 1.32, G was major allele.
There was no indication of interaction effect between PALB2 SNP
rs420259 and BRCA2 SNP rs9567552 in the Total SCOPE BD
sample (P > 0.05).
SCOPE schizophrenia case–control sample. None of the two
SNPs were associated with SCZ in our sample (P > 0.05) (Table II).
Meta-analysis. As seen in Table III, P-value for association
between PALB2 SNP rs420259 and BD in the combined sample was
1.2 105, and A was risk allele in all subsamples. A population
stratification between the SCOPE BD sample, the Icelandic BD
sample and the WTCCC BD sample was seen as indicated by the
differences in allele frequencies, but there was no indication of OR
heterogeneity, as the Breslow–Day test P-value was non-significant
(P ¼ 0.97).
Single SNP Association Data
No SNPs had genotype distributions in HWD in controls
(P < 0.01). The results are shown in Tables II and III and Table I
in Supplementary Material.
Hardy–Weinberg Equilibrium
Minor allele/
major allele
SNP conversion rate for BRCA2 in the SCOPE BD Subsample was
92.6%, reproducibility was 99.996% (there were 5 duplicate errors
in 124,684 duplicate genotype calls); and the average sample call
rate per SNP assay was 96.9%. Our BRCA2 tagSNPs in the SCOPE
BD Subsample covered 56% of the common variants with r2 0.8
and 95% with r2 0.5.
Total number
Genotyping and tagSNP Coverage
TABLE II. Nominally Significant PALB2 and BRCA2 SNPs in Single Marker Analyses of Scandinavian Bipolar Disorder (BD) and Schizophrenia (SCZ) Case–Control Samples
Breslow–Day tests, also implemented in PLINK, were undertaken.
For the combined BD sample (n ¼ 5,547/20,241) consisting of the
SCOPE/Icelandic/WTCCC BD sample and the STEP-UCL/EDDUB-STEP2 BD sample, we performed Fisher’s combined probability test to assess the P-value for association between BD and the
PALB2 SNP rs420259.
CI, confidence interval; CMH, Cochran–Mantel–Haenszel; OR, odds ratio.aP-value from Fisher’s combined probability test.
Total number Minor allele/ HWE
cases/controls major allele controls frequency frequency
OR (95% CI)
OR (95% CI)
SCOPE BD sample
0.84 (0.72–0.98)
Icelandic BD sample
0.88 (0.74–1.04)
WTCCC BD sample
0.00022 0.84 (0.76–0.92)
SCOPE/Icelandic/WTCCC BD sample 2,921/16,735
5.5 106 0.85 (0.79–0.91)
STEP-UCL/ED-DUB-STEP2 BD sample 2,558/3,274
1.2 105a
Combined BD sample
CMH test
Allele test
TABLE III. Meta-Analysis of PALB2 SNP rs420259 and Bipolar Disorder (BD)
Day test
WTCCC study [WTCCC, 2007], and a strong association between
the SNP rs9567552 in the new candidate gene BRCA2 and BD. We
did not find significant association between SCZ and these two
SNPs, which indicates no genetic overlap between BD and SCZ for
these gene variants.
The PALB2 SNP rs420259 has been investigated in two previous
association studies. The WTCCC study [WTCCC, 2007] found a
highly significant association with BD (P ¼ 6.3 108), whereas
another large collaborative study also reported a weak but nonsignificant (P ¼ 0.16) tendency to association in the same direction
[Ferreira et al., 2008]. Combining our results with these and
performing a meta-analysis in a sample of 5,547 BD cases and
20,241 controls, we found rs420259 to be significantly associated
with BD (P ¼ 1.2 105).
To our knowledge, this is the first hypothesis-driven association
study of BRCA2 and BD and SCZ, and the first study of BRCA2
SNP rs9567552 in these two disorders. The aforementioned
WTCCC study [WTCCC, 2007] did not find significant association
between 22 BRCA2 SNPs and BD (P > 0.05), but this study did not
investigate rs9567552. Rs9567552 is, according to, in LD with rs1799943 (r2 ¼ 0.96). Neither of these SNPs are
described in PubMed as associated with psychiatric disorders or
PALB2 was identified as a BD susceptibility gene in the WTCCC
study [WTCCC, 2007], but has been extensively studied as a factor
in cancer development. In a Chinese study the PALB2 SNP rs249954
was found to be associated with breast cancer (G/A, A risk allele)
[Chen et al., 2008]. This SNP is in linkage disequilibrium (LD) with
rs420259 (r2 ¼ 1.0 based on the Chinese HapMap population;
r2 ¼ 0.84 in CEU), which was associated with BD in the WTCCC
study [WTCCC, 2007] and replicated in the current study. According to, the G allele of rs249954 is in LD with A of
rs420259. Thus, the risk allele for breast cancer is in LD with the
protective allele for BD. This finding may be interpreted in several
ways, as we do not know which SNP is causatively associated with
these two phenotypes; different SNPs may be involved in different
diseases, or the same SNP may have protective effect for one
phenotype and increase the risk for developing the other phenotype. There may also be allele heterogeneity at the same locus in
different populations, which could imply that the risk allele for BD/
breast cancer in Europeans is the protective allele in the Chinese
population and vice versa [Hennah et al., 2008].
The mechanisms by which these two genes may be related to BD
are still unclear; but BRCA2 is expressed in the mouse brain, and was
shown to be important for normal neurogenesis, particularly in the
cerebellum [Frappart et al., 2007]. Cerebellum has been shown to be
involved in emotional processing, and cerebellar dysfunction has
been observed in BD [Konarski et al., 2005; Bolbecker et al., 2009].
Thus, it is possible that a dysfunction in BRCA2 and PALB2 leads to
altered neurogenesis in certain brain regions, which in turn may
increase the risk of developing BD. However, this remains
Taken together, the present findings suggest a causal relation
between PALB2 and BD and BRCA2 being a new BD candidate gene.
However, more studies are needed to investigate the association
between these genes and BD and SCZ, as well as potential molecular
We thank patients and controls for their participation in the study,
and the health professionals who facilitated our work. We also
thank Thomas D. Bjella for assistance with the database, Bente
Bennike, Knut-Erik Gylder, Trude Lien, and Elin Inderhaug for
molecular genetic technical assistance, as well as Kristina Larsson,
Per Lundmark, Tomas Axelsson, and Ann-Christine Syv€anen at the
SNP Technology Platform in Uppsala for performing the genotyping. The SNP Technology Platform is supported by Uppsala
University, Uppsala University Hospital and by the Knut and Alice
Wallenberg Foundation. The study was supported by grants to the
TOP study group from the University of Oslo, the Research Council
of Norway (#167153/V50, #163070/V50), the SouthEast Norway
Health Authority (#2004123), the Danish National Psychiatric
Research Foundation, the Lundbeck Foundation, the Stanley Medical Research Institute, the Wallenberg Foundation, the HUBIN
Project, and the Swedish Medical Research Council (2006-2992,
2006-986, 2008-2167). We would like to thank Dr. Hreinn Stefansson at deCODE Genetics and Dr. Pamela Sklar from Harvard
Medical School, Broad Institute for providing information from
replication samples. This study makes use of data generated by the
Wellcome Trust Case-Control Consortium. A full list of the investigators who contributed to the generation of the data is available
from Funding for the project was provided by
the Wellcome Trust under award 076113.
Bolbecker AR, Mehta C, Johannesen JK, Edwards CR, O’Donnell BF,
Shekhar A, Nurnberger JI, Steinmetz JE, Hetrick WP. 2009. Eyeblink
conditioning anomalies in bipolar disorder suggest cerebellar dysfunction. Bipolar Disord 11(1):19–32.
Chen P, Liang J, Wang Z, Zhou X, Chen L, Li M, Xie D, Hu Z, Shen H,
Wang H. 2008. Association of common PALB2 polymorphisms with
breast cancer risk: A case-control study. Clin Cancer Res 14(18):
Craddock N, Khodel V, Van EP, Reich T. 1995. Mathematical limits of
multilocus models: The genetic transmission of bipolar disorder. Am J
Hum Genet 57(3):690–702.
de Bakker PI, Yelensky R, Pe’er I, Gabriel SB, Daly MJ, Altshuler D. 2005.
Efficiency and power in genetic association studies. Nat Genet 37(11):
Ferreira MA, O’Donovan MC, Meng YA, Jones IR, Ruderfer DM, Jones L,
Fan J, Kirov G, Perlis RH, Green EK, Smoller JW, Grozeva D, Stone J,
Nikolov I, Chambert K, Hamshere ML, Nimgaonkar VL, Moskvina V,
Thase ME, Caesar S, Sachs GS, Franklin J, Gordon-Smith K, Ardlie KG,
Gabriel SB, Fraser C, Blumenstiel B, Defelice M, Breen G, Gill M, Morris
DW, Elkin A, Muir WJ, McGhee KA, Williamson R, MacIntyre DJ,
Maclean AW, St CD, Robinson M, Van BM, Pereira AC, Kandaswamy R,
McQuillin A, Collier DA, Bass NJ, Young AH, Lawrence J, Nicol F I,
Anjorin A, Farmer A, Curtis D, Scolnick EM, McGuffin P, Daly MJ,
Corvin AP, Holmans PA, Blackwood DH, Gurling HM, Owen MJ, Purcell
SM, Sklar P, Craddock N, 2008. Collaborative genome-wide association
analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat
Genet 40(9):1056–1058.
Frappart PO, Lee Y, Lamont J, McKinnon PJ. 2007. BRCA2 is required
for neurogenesis and suppression of medulloblastoma. EMBO J 26(11):
Hansen T, Olsen L, Lindow M, Jakobsen KD, Ullum H, Jonsson E,
Andreassen OA, Djurovic S, Melle I, Agartz I, Hall H, Timm S, Wang
AG, Werge T. 2007. Brain expressed microRNAs implicated in schizophrenia etiology. PLoS ONE 2(9):e873.
Hennah W, Thomson P, McQuillin A, Bass N, Loukola A, Anjorin A,
Blackwood D, Curtis D, Deary IJ, Harris SE, Isometsa ET, Lawrence J,
Lonnqvist J, Muir W, Palotie A, Partonen T, Paunio T, Pylkko E,
Robinson M, Soronen P, Suominen K, Suvisaari J, Thirumalai S, Clair
DS, Gurling H, Peltonen L, Porteous D. 2008. DISC1 association,
heterogeneity and interplay in schizophrenia and bipolar disorder. Mol
Psychiatry 14(9):865–873.
Kahler AK, Djurovic S, Kulle B, Jonsson EG, Agartz I, Hall H, Opjordsmoen
S, Jakobsen KD, Hansen T, Melle I, Werge T, Steen VM, Andreassen OA.
2008. Association analysis of schizophrenia on 18 genes involved in
neuronal migration: MDGA1 as a new susceptibility gene. Am J Med
Genet Part B 147B(7):1089–1100.
Keshavan MS, Tandon R, Boutros NN, Nasrallah HA. 2008. Schizophrenia,
‘‘just the facts’’: What we know in 2008 Part 3: Neurobiology. Schizophr
Res 106(2–3):89–107.
Konarski JZ, McIntyre RS, Grupp LA, Kennedy SH. 2005. Is the cerebellum
relevant in the circuitry of neuropsychiatric disorders? J Psychiatry
Neurosci 30(3):178–186.
Lichtenstein P, Yip BH, Bjork C, Pawitan Y, Cannon TD, Sullivan PF,
Hultman CM. 2009. Common genetic determinants of schizophrenia
and bipolar disorder in Swedish families: A population-based study.
Lancet 373(9659):234–239.
McGuffin P, Farmer A, Harvey I. 1991. A polydiagnostic application of
operational criteria in studies of psychotic illness. Development and
reliability of the OPCRIT system. Arch Gen Psychiatry 48(8):764–
Moskvina V, Craddock N, Holmans P, Nikolov I, Pahwa JS, Green E, Owen
MJ, O’Donovan MC. 2009. Gene-wide analyses of genome-wide association data sets: Evidence for multiple common risk alleles for schizophrenia and bipolar disorder and for overlap in genetic risk. Mol Psychiatry
Newberg AR, Catapano LA, Zarate CA, Manji HK. 2008. Neurobiology of
bipolar disorder. Expert Rev Neurother 8(1):93–110.
Owen MJ, Williams HJ, O’Donovan MC. 2009. Schizophrenia
genetics: Advancing on two fronts. Curr Opin Genet Dev 19(3):266–
Peters L, Andrews G. 1995. Procedural validity of the computerized version
of the Composite International Diagnostic Interview (CIDI-Auto) in the
anxiety disorders. Psychol Med 25(6):1269–1280.
Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D,
Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC. 2007. PLINK: A tool set
for whole-genome association and population-based linkage analyses.
Am J Hum Genet 81(3):559–575.
Rahman N, Seal S, Thompson D, Kelly P, Renwick A, Elliott A, Reid S,
Spanova K, Barfoot R, Chagtai T, Jayatilake H, McGuffog L, Hanks S,
Evans DG, Eccles D, Easton DF, Stratton MR. 2007. PALB2, which
encodes a BRCA2-interacting protein, is a breast cancer susceptibility
gene. Nat Genet 39(2):165–167.
Sklar P, Smoller JW, Fan J, Ferreira MA, Perlis RH, Chambert K,
Nimgaonkar VL, McQueen MB, Faraone SV, Kirby A, de Bakker PI,
Ogdie MN, Thase ME, Sachs GS, Todd-Brown K, Gabriel SB, Sougnez
C, Gates C, Blumenstiel B, Defelice M, Ardlie KG, Franklin J, Muir
WJ, McGhee KA, MacIntyre DJ, McLean A, VanBeck M, McQuillin A,
Bass NJ, Robinson M, Lawrence J, Anjorin A, Curtis D, Scolnick EM,
Daly MJ, Blackwood DH, Gurling HM, Purcell SM. 2008. Wholegenome association study of bipolar disorder. Mol Psychiatry 13(6):
Spitzer REJ. 1977. The Schedule for Affective Disorders and Schizophrenia,
Lifetime Version. New York: New York State Psychiatric Institute.
Spitzer RL, Endicott J, Robins E. 1978. Research diagnostic criteria:
Rationale and reliability. Arch Gen Psychiatry 35(6):773–782.
Spitzer RL, Williams JB, Gibbon M, First MB. 1992. The Structured Clinical
Interview for DSM-III-R (SCID). I: History, rationale, and description.
Arch Gen Psychiatry 49(8):624–629.
Thorgeirsson TE, Oskarsson H, Desnica N, Kostic JP, Stefansson JG,
Kolbeinsson H, Lindal E, Gagunashvili N, Frigge ML, Kong A, Stefansson
K, Gulcher JR. 2003. Anxiety with panic disorder linked to chromosome
9q in Iceland. Am J Hum Genet 72(5):1221–1230.
Tutt A, Ashworth A. 2002. The relationship between the roles of BRCA
genes in DNA repair and cancer predisposition. Trends Mol Med 8(12):
Wittchen HU, Zhao S, Abelson JM, Abelson JL, Kessler RC. 1996. Reliability
and procedural validity of UM-CIDI DSM-III-R phobic disorders.
Psychol Med 26(6):1169–1177.
WTCCC. 2007. Genome-wide association study of 14,000 cases of seven
common diseases and 3,000 shared controls. Nature 447(7145):661–678.
Xia B, Sheng Q, Nakanishi K, Ohashi A, Wu J, Christ N, Liu X, Jasin M,
Couch FJ, Livingston DM. 2006. Control of BRCA2 cellular and clinical
functions by a nuclear partner, PALB2. Mol Cell 22(6):719–729.
Без категории
Размер файла
114 Кб
brca, associations, disorder, caseцcontrol, analysis, samples, bipolar, palb2, schizophrenia, scandinavian
Пожаловаться на содержимое документа