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5-HT2C receptor and MAO-A interaction analysis: no association with suicidal behaviour in bipolar patients.

https://arctichealth.org/en/permalink/ahliterature157011
Source
Eur Arch Psychiatry Clin Neurosci. 2008 Oct;258(7):428-33
Publication Type
Article
Date
Oct-2008
Author
Vincenzo De Luca
Subi Tharmaligam
John Strauss
James L Kennedy
Author Affiliation
Dept. of Psychiatry, University of Toronto, 250 College Street, R-30, Toronto (ON), Canada M5T 1R8. vincenzo_deluca@camh.net
Source
Eur Arch Psychiatry Clin Neurosci. 2008 Oct;258(7):428-33
Date
Oct-2008
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Aged
Bipolar Disorder - genetics - psychology
Canada
Family Health
Female
Gene Frequency
Genes, X-Linked
Genetic Predisposition to Disease
Genotype
Haplotypes
Humans
Male
Middle Aged
Monoamine Oxidase - genetics
Nuclear Family
Polymorphism, Single Nucleotide
Receptor, Serotonin, 5-HT2C - genetics
Suicide, Attempted - psychology
Young Adult
Abstract
The serotonin 2C (HTR2C) receptor has been implicated in suicide-related behaviours, however there are not many studies to date about HTR2C and suicidality. We studied HTR2C haplotypes in suicide attempters, where our sample composed of 306 families with at least one member affected by bipolar disorder. HTR2C (Cys23Ser and a common STR in the promoter) variants were analyzed with respect to attempter status and the severity of suicidal behaviour. The X-linked haplotype analysis in relation to suicide attempt did not reveal any significant association. Furthermore, we performed a particular gene-gene interaction for the X-linked serotonergic genes (HTR2C and MAOA), and found no association among this intergenic haplotype combination and suicidal behaviour in bipolar disorder.
PubMed ID
18504633 View in PubMed
Less detail

Association between schizophrenia and the syntaxin 1A gene.

https://arctichealth.org/en/permalink/ahliterature179475
Source
Biol Psychiatry. 2004 Jul 1;56(1):24-9
Publication Type
Article
Date
Jul-1-2004
Author
Albert H C Wong
Joseph Trakalo
Olga Likhodi
Muneeb Yusuf
Antonio Macedo
Maria-Helena Azevedo
Tim Klempan
Michele T Pato
William G Honer
Carlos N Pato
Hubert H M Van Tol
James L Kennedy
Author Affiliation
Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Source
Biol Psychiatry. 2004 Jul 1;56(1):24-9
Date
Jul-1-2004
Language
English
Publication Type
Article
Keywords
Adult
Antigens, Surface - genetics
Case-Control Studies
Chromosome Mapping
Female
Genetic Linkage
Genetic Predisposition to Disease - genetics
Haplotypes
Humans
Introns - genetics
Male
Nerve Tissue Proteins - genetics
Ontario - epidemiology
Pedigree
Polymorphism, Single Nucleotide
Portugal - epidemiology
Reference Values
Schizophrenia - epidemiology - genetics
Syntaxin 1
Abstract
Both microarray and candidate molecule studies have demonstrated that protein and mRNA expression of syntaxin and other genes involved in synaptic function are altered in the cerebral cortex of patients with schizophrenia.
Genetic association between polymorphic markers in the syntaxin 1A gene and schizophrenia was assessed in a matched case-control sample of 192 pairs, and in an independent sample of 238 nuclear families.
In the family-based sample, a significant genetic association was found between schizophrenia and one of the four single nucleotide polymorphisms (SNPs) tested: an intron 7 SNP (transmission disequilibrium test [TDT] chi(2) = 5.898; df = 1; p =.015, family-based association test [FBAT] z = 2.280, p =.023). When the results for the TDT and case-control analyses were combined, the association was stronger (n = 430; z(c) = 2.859; p =.004). Haplotype analysis supported the association with several significant values that appear to be driven by the intron 7 SNP.
The results should be treated with caution until replicated, but this is the first report of a genetic association between syntaxin 1A and schizophrenia.
PubMed ID
15219469 View in PubMed
Less detail

Association between the seven-repeat allele of the dopamine-4 receptor gene (DRD4) and spontaneous food intake in pre-school children.

https://arctichealth.org/en/permalink/ahliterature106526
Source
Appetite. 2014 Feb;73:15-22
Publication Type
Article
Date
Feb-2014
Author
Patrícia Pelufo Silveira
André Krumel Portella
James L Kennedy
Hélène Gaudreau
Caroline Davis
Meir Steiner
Claudio N Soares
Stephen G Matthews
Marla B Sokolowski
Laurette Dubé
Eric B Loucks
Jill Hamilton
Michael J Meaney
Robert D Levitan
Author Affiliation
Department of Psychiatry and Neurology, McGill University, Douglas Mental Health University Institute, Canada; Departamento de Pediatria, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul Ramiro Barcelos, 2350 Largo Eduardo Zaccaro Faraco, 90035-903 Porto Alegre, RS, Brazil. Electronic address: 00032386@ufrgs.br.
Source
Appetite. 2014 Feb;73:15-22
Date
Feb-2014
Language
English
Publication Type
Article
Keywords
Alleles
Body mass index
Canada
Child, Preschool
Diet
Eating
Energy Intake - genetics
Female
Food Habits
Food Preferences
Genotype
Humans
Hyperphagia - genetics
Male
Obesity - genetics
Receptors, Dopamine D4 - genetics
Sex Factors
Snacks
Abstract
Studies in adults show associations between the hypofunctional seven-repeat allele (7R) of the dopamine-4 receptor gene (DRD4), increased eating behaviour and/or obesity, particularly in females. We examined whether 7R is associated with total caloric intake and/or food choices in pre-schoolers.
150 four-year-old children taking part in a birth cohort study in Canada were administered a snack test meal in a laboratory setting. Mothers also filled out a food frequency questionnaire to address childrens' habitual food consumption. Total caloric and individual macronutrient intakes during the snack meal and specific types of foods as reported in the food diaries were compared across 7R allele carriers vs. non-carriers, using current BMI as a co-variate.
We found significant sex by genotype interactions for fat and protein intake during the snack test. Post hoc testing revealed that in girls, but not boys, 7R carriers ate more fat and protein than did non-carriers. Based on the food diaries, across both sexes, 7R carriers consumed more portions of ice cream and less vegetables, eggs, nuts and whole bread, suggesting a less healthy pattern of habitual food consumption.
The 7R allele of DRD4 influences macronutrient intakes and specific food choices as early as four years of age. The specific pattern of results further suggests that prior associations between the 7R allele and adult overeating/obesity may originate in food choices observable in the preschool years. Longitudinal follow-up of these children will help establish the relevance of these findings for obesity risk and prevention.
PubMed ID
24153108 View in PubMed
Less detail

Association of functional variants in the dopamine D2-like receptors with risk for gambling behaviour in healthy Caucasian subjects.

https://arctichealth.org/en/permalink/ahliterature143707
Source
Biol Psychol. 2010 Sep;85(1):33-7
Publication Type
Article
Date
Sep-2010
Author
Daniela S S Lobo
Renan P Souza
Ryan P Tong
David M Casey
David C Hodgins
Garry J Smith
Rob J Williams
Don P Schopflocher
Rob T Wood
Nady el-Guebaly
James L Kennedy
Author Affiliation
Neurogenetics Section, Neuroscience Department, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. daniela_lobo@camh.net
Source
Biol Psychol. 2010 Sep;85(1):33-7
Date
Sep-2010
Language
English
Publication Type
Article
Keywords
Adult
Canada
Chi-Square Distribution
Chromosomes, Human, Pair 11
European Continental Ancestry Group - genetics
Female
Gambling - psychology
Gene Frequency
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Humans
Impulse Control Disorders - genetics
Linkage Disequilibrium
Male
Middle Aged
Polymorphism, Genetic - genetics
Abstract
Pathological gambling (PG) is an impulse control disorder with suggestive genetic vulnerability component. We evaluated the association of genetic variants in the dopaminergic receptor genes (DRD1-3s) with risk for gambling in healthy subjects using the Canadian Problem Gambling Index (CPGI). Healthy Caucasian subjects who had gambled at least once in their lifetime (n=242) were included in the analysis. Gender was not associated with the CPGI, while younger age was associated with higher CPGI scores. We have found that none of the single polymorphisms investigated on DRD1 and DRD3 were associated with CPGI scores in healthy subjects. However, we observed trends for association on the TaqIA/rs1800497 polymorphism (P=0.10) and the haplotype flanking DRD2 (G/C/A rs11604671/rs4938015/rs2303380; P=0.06). Both trends were associated with lower CPGI score. Our results provide further evidence for the role of dopamine D2-like receptor in addiction susceptibility.
PubMed ID
20452395 View in PubMed
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Dopaminergic system genes in childhood aggression: possible role for DRD2.

https://arctichealth.org/en/permalink/ahliterature137798
Source
World J Biol Psychiatry. 2012 Jan;13(1):65-74
Publication Type
Article
Date
Jan-2012
Author
Clement C Zai
Sahar Ehtesham
Esther Choi
Behdin Nowrouzi
Vincenzo de Luca
Larisa Stankovich
Kristen Davidge
Natalie Freeman
Nicole King
James L Kennedy
Joseph H Beitchman
Author Affiliation
Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, Canada.
Source
World J Biol Psychiatry. 2012 Jan;13(1):65-74
Date
Jan-2012
Language
English
Publication Type
Article
Keywords
Aggression - physiology
Canada
Child
Child Behavior Disorders - genetics
Dopamine - genetics
Dopamine Plasma Membrane Transport Proteins - genetics
Female
Genetic Predisposition to Disease
Humans
Male
Polymorphism, Genetic
Receptors, Dopamine D2 - genetics
Receptors, Dopamine D4 - genetics
Abstract
Excessive or deficient levels of extracellular dopamine have been hypothesized to contribute to a broad spectrum of mood, motor, and thought abnormalities, and dopaminergic system genes have been implicated in aggressive behaviour from animal and human studies. OBJECTIVE. We examined selected members of the dopaminergic system genes for association with child aggression.
We analyzed polymorphisms in the dopamine transporter DAT1/SLC6A3, dopamine receptor DRD2, and DRD4 genes in our sample of pervasive childhood aggression consisting of 144 cases paired with 144 healthy controls, matched for sex and ethnicity.
Aggressive children were significantly more likely to have the at least one copy of the G allele for the DRD2 A-241G polymorphism (genotypic P=0.02; allelic P=0.01). The DRD2 rs1079598 CC genotype was overrepresented in aggressive children compared to controls (genotype P=0.04). The DRD2 TaqIA T allele (P=0.01) and the TT genotype (P=0.01) were also significantly overrepresented in aggressive children.
Our preliminary results suggest that three polymorphisms in DRD2 are associated with childhood aggression. Future studies are required to replicate the current results and to further explore the relationship between the dopamine system and aggressive behaviour in children.
PubMed ID
21247255 View in PubMed
Less detail

Genome-wide association study of bipolar disorder in Canadian and UK populations corroborates disease loci including SYNE1 and CSMD1.

https://arctichealth.org/en/permalink/ahliterature105424
Source
BMC Med Genet. 2014;15:2
Publication Type
Article
Date
2014
Author
Wei Xu
Sarah Cohen-Woods
Qian Chen
Abdul Noor
Jo Knight
Georgina Hosang
Sagar V Parikh
Vincenzo De Luca
Federica Tozzi
Pierandrea Muglia
Julia Forte
Andrew McQuillin
Pingzhao Hu
Hugh M D Gurling
James L Kennedy
Peter McGuffin
Anne Farmer
John Strauss
John B Vincent
Author Affiliation
Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), R-32, 250 College Street, Toronto, ON M5T 1R8, Canada. john.vincent@camh.ca.
Source
BMC Med Genet. 2014;15:2
Date
2014
Language
English
Publication Type
Article
Keywords
Bipolar Disorder - genetics
Canada
Cohort Studies
Genetic Loci - genetics
Genome-Wide Association Study
Genotype
Great Britain
Humans
Membrane Proteins - genetics
Nerve Tissue Proteins - genetics
Nuclear Proteins - genetics
Pedigree
Reproducibility of Results
Young Adult
Abstract
Recently, genome-wide association studies (GWAS) for cases versus controls using single nucleotide polymorphism microarray data have shown promising findings for complex neuropsychiatric disorders, including bipolar disorder (BD).
Here we describe a comprehensive genome-wide study of bipolar disorder (BD), cross-referencing analysis from a family-based study of 229 small families with association analysis from over 950 cases and 950 ethnicity-matched controls from the UK and Canada. Further, loci identified in these analyses were supported by pathways identified through pathway analysis on the samples.
Although no genome-wide significant markers were identified, the combined GWAS findings have pointed to several genes of interest that support GWAS findings for BD from other groups or consortia, such as at SYNE1 on 6q25, PPP2R2C on 4p16.1, ZNF659 on 3p24.3, CNTNAP5 (2q14.3), and CDH13 (16q23.3). This apparent corroboration across multiple sites gives much confidence to the likelihood of genetic involvement in BD at these loci. In particular, our two-stage strategy found association in both our combined case/control analysis and the family-based analysis on 1q21.2 (closest gene: sphingosine-1-phosphate receptor 1 gene, S1PR1) and on 1q24.1 near the gene TMCO1, and at CSMD1 on 8p23.2, supporting several previous GWAS reports for BD and for schizophrenia. Pathway analysis suggests association of pathways involved in calcium signalling, neuropathic pain signalling, CREB signalling in neurons, glutamate receptor signalling and axonal guidance signalling.
The findings presented here show support for a number of genes previously implicated genes in the etiology of BD, including CSMD1 and SYNE1, as well as evidence for previously unreported genes such as the brain-expressed genes ADCY2, NCALD, WDR60, SCN7A and SPAG16.
Notes
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PubMed ID
24387768 View in PubMed
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Haplotype association study between DRD1 gene and bipolar type I affective disorder in two samples from Canada and Sardinia.

https://arctichealth.org/en/permalink/ahliterature166880
Source
Am J Med Genet B Neuropsychiatr Genet. 2007 Mar 5;144B(2):237-41
Publication Type
Article
Date
Mar-5-2007
Author
Maria Del Zompo
Vincenzo De Luca
Giovanni Severino
Xingqun Ni
Stefania Mulas
Donatella Congiu
Maria Paola Piccardi
James L Kennedy
Author Affiliation
Department of Neurosciences B.B. Brodie, Section of Clinical Pharmacology, Center of Clinical Psychopharmacology, University of Cagliari, Cagliari, Italy. delzompo@unica.it
Source
Am J Med Genet B Neuropsychiatr Genet. 2007 Mar 5;144B(2):237-41
Date
Mar-5-2007
Language
English
Publication Type
Article
Keywords
Adult
Alleles
Bipolar Disorder - genetics
Canada
Case-Control Studies
Female
Genetic Predisposition to Disease
Haplotypes
Humans
Italy
Male
Polymorphism, Single Nucleotide - genetics
Receptors, Dopamine D1 - genetics
Risk factors
Abstract
Based on the dopaminergic hypothesis, the dopamine D(1) receptor gene (DRD1) is considered to be a good candidate gene involved in the susceptibility of bipolar disorder (BP). Genetic association between three DRD1 single nucleotide polymorphisms (SNPs) (-800T/C, -48A/G, and 1403T/C) and bipolar type I (BP I) disorder was performed in a case-control sample of Sardinian origin (170 BP I and 209 controls) and in an enlarged sample (229 families) of BP I trios from Toronto. The haplotype analyses generated significant global chi-square in both samples (P-value 0.024 in Toronto and 0.00042 in Sardinian). The main representative haplotypes in both samples were the -800T/-48A/1403C and the -800C/-48G/1403T. Considering each group individually, the -800C/-48G/1403T was transmitted more frequently from parents to BP I probands in Toronto sample (nominally P-value = 0.047) and was more frequent in cases than in control subjects in Sardinian sample although showing no significant evidence of association (nominally P-value = 0.16) When the estimated haplotype counts of both samples were combined, the global chi(2) was significant (P-value = 0.00085) and the nominal P-value for the haplotype -800C/-48G/1403T was 0.01. The fact that the same haplotype shows a similar trend for association in samples originating from different ethnic backgrounds seems to imply that the -800C/-48G/1403T haplotype may be considered as a risk factor for BP I disorder.
PubMed ID
17066478 View in PubMed
Less detail

Human p53 tumor suppressor gene (TP53) and schizophrenia: case-control and family studies.

https://arctichealth.org/en/permalink/ahliterature173686
Source
Neurosci Lett. 2005 Nov 18;388(3):173-8
Publication Type
Article
Date
Nov-18-2005
Author
Xingqun Ni
Joseph Trakalo
Jose Valente
Maria H Azevedo
Michelle T Pato
Carlos N Pato
James L Kennedy
Author Affiliation
Neuroscience Research Department, Neurogenetics Section, Centre for Addiction and Mental Health, 250 College Street, Toronto, Canada M5T 1R8.
Source
Neurosci Lett. 2005 Nov 18;388(3):173-8
Date
Nov-18-2005
Language
English
Publication Type
Article
Keywords
Brain Chemistry - genetics
Case-Control Studies
DNA Mutational Analysis
Female
Gene Frequency - genetics
Genetic Predisposition to Disease - genetics
Genetic Testing
Genotype
Haplotypes
Humans
Linkage Disequilibrium - genetics
Male
Ontario - epidemiology
Polymorphism, Genetic - genetics
Portugal - epidemiology
Schizophrenia - epidemiology - genetics - metabolism
Tumor Suppressor Protein p53 - genetics
Abstract
The human p53 tumor suppressor gene (TP53) is considered as a candidate susceptibility gene for schizophrenia because of its functions in neurodevelopment. To test for an association between TP53 and schizophrenia, both the case-control study and the transmission disequilibrium test (TDT) were performed on genotype data from eight polymorphisms in TP53. Our samples included 286 Toronto schizophrenia cases and 264 controls, and 163 Portuguese nuclear families. In the Toronto case-control study significant differences of allele frequencies of the CAA Ins/Del (p=0.027) and the 16bp Ins/Del (p=0.022) were detected. In TDT analysis we found significant differences for transmission of the CAA Ins/Del (p=0.017) in Portuguese schizophrenia families. Haplotype analysis also showed a significant association between TP53 and schizophrenia. These results provide further evidence that TP53 may play a role in the pathogenesis of schizophrenia.
PubMed ID
16039051 View in PubMed
Less detail

Myelin oligodendrocyte glycoprotein (MOG) gene is associated with obsessive-compulsive disorder.

https://arctichealth.org/en/permalink/ahliterature179104
Source
Am J Med Genet B Neuropsychiatr Genet. 2004 Aug 15;129B(1):64-8
Publication Type
Article
Date
Aug-15-2004
Author
Gwyneth Zai
Yarema B Bezchlibnyk
Margaret A Richter
Paul Arnold
Eliza Burroughs
Cathy L Barr
James L Kennedy
Author Affiliation
Neurogenetics Section, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Source
Am J Med Genet B Neuropsychiatr Genet. 2004 Aug 15;129B(1):64-8
Date
Aug-15-2004
Language
English
Publication Type
Article
Keywords
Adult
Age of Onset
Alleles
Canada
DNA - genetics - isolation & purification
Female
Gene Frequency
Genotype
Humans
Linkage Disequilibrium
Male
Middle Aged
Myelin Proteins
Myelin-Associated Glycoprotein - genetics
Myelin-Oligodendrocyte Glycoprotein
Nuclear Family
Obsessive-Compulsive Disorder - genetics
Polymorphism, Genetic
Abstract
Obsessive-compulsive disorder (OCD) is a severe neuropsychiatric disorder with a strong genetic component, and may involve autoimmune processes. Support for this latter hypothesis comes from the identification of a subgroup of children, described by the term pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS), with onset of OCD symptoms following streptococcal infections. Genes involved in immune response therefore represent possible candidate genes for OCD, including the myelin oligodendrocyte glycoprotein (MOG) gene, which plays an important role in mediating the complement cascade in the immune system. Four polymorphisms in the MOG gene, a dinucleotide CA repeat (MOG2), a tetranucleotide TAAA repeat (MOG4), and 2 intronic single nucleotide polymorphisms, C1334T and C10991T, were investigated for the possibility of association with OCD using 160 nuclear families with an OCD proband. We examined the transmission of alleles of these four polymorphisms with the transmission disequilibrium test (TDT). A biased transmission of the 459-bp allele (allele 2: chi2 = 5.255, P = 0.022) of MOG4 was detected, while MOG2, C1334T, and C10991T showed no statistically significant bias in the transmission of alleles. The transmission of the C1334T.MOG2.C10991T.MOG4 haplotype 1.13.2.2 (chi2 = 6.426, P = 0.011) was also significant. Quantitative analysis using the family-based association test (FBAT) was significant for MOG4 in total Yale-Brown Obsessive-Compulsive Scale severity score (allele 2: z = 2.334, P = 0.020). Further investigations combining genetic, pathological, and pharmacological strategies, are warranted.
PubMed ID
15274043 View in PubMed
Less detail

N-methyl-D-aspartate receptor NR1 subunit gene (GRIN1) in schizophrenia: TDT and case-control analyses.

https://arctichealth.org/en/permalink/ahliterature185731
Source
Am J Med Genet B Neuropsychiatr Genet. 2003 May 15;119B(1):24-7
Publication Type
Article
Date
May-15-2003
Author
Livia Martucci
Albert H C Wong
Joseph Trakalo
Tasha Cate-Carter
Gregory W H Wong
Fabio M Macciardi
James L Kennedy
Author Affiliation
Neurogenetics Section, CAMH, Clarke Division, University of Toronto, Toronto, Ontario, Canada.
Source
Am J Med Genet B Neuropsychiatr Genet. 2003 May 15;119B(1):24-7
Date
May-15-2003
Language
English
Publication Type
Article
Keywords
Age of Onset
Amino Acid Substitution
Analysis of Variance
Canada
Case-Control Studies
Family Health
Gene Frequency
Genotype
Haplotypes
Humans
Inheritance Patterns
Linkage Disequilibrium
Polymorphism, Single Nucleotide
Receptors, N-Methyl-D-Aspartate - genetics
Schizophrenia - genetics
Abstract
The N-methyl-d-aspartate glutamate receptors (NMDAR) act in the CNS as regulators of the release of neurotransmitters such as dopamine, noradrenaline, acetylcholine, and GABA. It has been suggested that a weakened glutamatergic tone increases the risk of sensory overload and of exaggerated responses in the monoaminergic system, which is consistent with the symptomatology of schizophrenia. We studied two silent polymorphisms in GRIN1. GRIN1/1 is a G/C substitution localized on the 5' untranslated region; GRIN1/10 is an A/G substitution localized in exon 6 of GRIN1. Minor allele frequencies in our sample were calculated to be 0.05 and 0.2 respectively. We genotyped 86 nuclear families and 91 ethnically matched case-control pairs. Both samples were collected from the Toronto area. We tested the hypothesis that GRIN1 polymorphisms were associated with schizophrenia using the transmission disequilibrium test (TDT) and comparing allele frequencies between cases and controls. The results are as follows: GRIN1/1: chi(2) = 2.19, P = 0.14; GRIN1/10: chi(2) = 1.5, P = 0.22. For the case-control sample: GRIN1/1: chi(2) = 0.013, P = 0.908; GRIN1/10: chi(2) = 0.544, P = 0.461. No significant results were obtained. Haplotype analyses showed a borderline significant result for the 2,1 haplotype (chi(2) = 3.86, P-value = 0.049). An analysis of variance (ANOVA) to evaluate the association between genetic makeup and age at onset was performed, with no significant results: GRIN1/1, F[df = 2] = 0.42, P-value = 0.659; GRIN1/10, F[df = 2] = 0.16, P-value = 0.853. We are currently collecting additional samples to increase the power of the analyses.
PubMed ID
12707933 View in PubMed
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