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X Xu,
E A Duman,
R Anney, K Brookes,
B Franke,
K Zhou,
C Buschgens,
W Chen,
H Christiansen,
J Eisenberg, [......],
F Mulas,
R D Oades,
H Roeyers,
A Rothenberger,
J Sergeant,
E Sonuga-Barke,
H C Steinhausen,
E Taylor,
S V Faraone,
P Asherson
American Journal of Medical Genetics Part B Neuropsychiatric Genetics 03/2009; · 3.70 Impact Factor
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X. Xu,
E. Aysimi,
R. Anney, K. Brookes,
B. Franke,
K. Zhou,
C. Buschgens,
W. Chen,
H. Christiansen,
J. Eisenberg, [......],
F. Mulas,
R.D. Oades,
H. Roeyers,
A. Rothenberger,
J. Sergeant,
E. Sonuga-Barke,
H.-C. Steinhausen,
E. Taylor,
S.V. Faraone,
P. Asherson
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[hide abstract]
ABSTRACT: Several independent studies have reported association between serotonin transporter gene (SLC6A4) polymorphisms and attention deficit hyperactivity disorder (ADHD). Five studies found evidence for association between the long-allele of a 44-bp insertion/deletion polymorphism (5-HTTLPR) and ADHD. Another two studies corroborated this finding while a further six studies did not find such an association. For a second polymorphism within the gene, a variable number tandem repeat (VNTR) within intron 2, one study demonstrated that the 12/12 genotype was significantly less frequent in ADHD cases compared to controls, while a second study found that the 12-allele was preferentially transmitted to offspring affected with ADHD. To provide further clarification of the reported associations, we investigated the association of these two markers with ADHD in a sample of 1,020 families with 1,166 combined type ADHD cases for the International Multi-Centre ADHD Genetics project, using the Transmission Disequilibrium Test. Given the large body of work supporting the association of the promoter polymorphism and mood disorders, we further analyzed the group of subjects with ADHD plus mood disorder separately. No association was found between either of the two markers and ADHD in our large multisite study or with depression within the sample of ADHD cases. © 2008 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics 10/2008; 147B(7):1306 - 1309. · 3.70 Impact Factor
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X Xu,
E A Duman,
E Aysimi,
R Anney, K Brookes,
B Franke,
K Zhou,
C Buschgens,
W Chen,
H Christiansen, [......],
F Mulas,
R D Oades,
H Roeyers,
A Rothenberger,
J Sergeant,
E Sonuga-Barke,
H-C Steinhausen,
E Taylor,
S V Faraone,
P Asherson
[show abstract]
[hide abstract]
ABSTRACT: Several independent studies have reported association between serotonin transporter gene (SLC6A4) polymorphisms and attention deficit hyperactivity disorder (ADHD). Five studies found evidence for association between the long-allele of a 44-bp insertion/deletion polymorphism (5-HTTLPR) and ADHD. Another two studies corroborated this finding while a further six studies did not find such an association. For a second polymorphism within the gene, a variable number tandem repeat (VNTR) within intron 2, one study demonstrated that the 12/12 genotype was significantly less frequent in ADHD cases compared to controls, while a second study found that the 12-allele was preferentially transmitted to offspring affected with ADHD. To provide further clarification of the reported associations, we investigated the association of these two markers with ADHD in a sample of 1,020 families with 1,166 combined type ADHD cases for the International Multi-Centre ADHD Genetics project, using the Transmission Disequilibrium Test. Given the large body of work supporting the association of the promoter polymorphism and mood disorders, we further analyzed the group of subjects with ADHD plus mood disorder separately. No association was found between either of the two markers and ADHD in our large multisite study or with depression within the sample of ADHD cases.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics 06/2008; 147B(7):1306-9. · 3.70 Impact Factor
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P Asherson,
K Zhou,
R J L Anney,
B Franke,
J Buitelaar,
R Ebstein,
M Gill,
M Altink,
R Arnold,
F Boer, [......],
I Manor,
A Miranda,
R D Oades,
H Roeyers,
A Rothenberger,
J Sergeant,
H-C Steinhausen,
E Taylor,
M Thompson,
S V Faraone
[show abstract]
[hide abstract]
ABSTRACT: As part of the International Multi-centre ADHD Genetics project we completed an affected sibling pair study of 142 narrowly defined Diagnostic and Statistical Manual of Mental Disorders, fourth edition combined type attention deficit hyperactivity disorder (ADHD) proband-sibling pairs. No linkage was observed on the most established ADHD-linked genomic regions of 5p and 17p. We found suggestive linkage signals on chromosomes 9 and 16, respectively, with the highest multipoint nonparametric linkage signal on chromosome 16q23 at 99 cM (log of the odds, LOD=3.1) overlapping data published from the previous UCLA (University of California, Los Angeles) (LOD>1, approximately 95 cM) and Dutch (LOD>1, approximately 100 cM) studies. The second highest peak in this study was on chromosome 9q22 at 90 cM (LOD=2.13); both the previous UCLA and German studies also found some evidence of linkage at almost the same location (UCLA LOD=1.45 at 93 cM; German LOD=0.68 at 100 cM). The overlap of these two main peaks with previous findings suggests that loci linked to ADHD may lie within these regions. Meta-analysis or reanalysis of the raw data of all the available ADHD linkage scan data may help to clarify whether these represent true linked loci.
Molecular psychiatry 05/2008; 13(5):514-21. · 15.05 Impact Factor
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K Brookes,
X Xu,
W Chen,
K Zhou,
B Neale,
N Lowe,
R Anney,
R Aneey,
B Franke,
M Gill, [......],
R D Oades,
R Plomin,
H Roeyers,
A Rothenberger,
J Sergeant,
H-C Steinhausen,
E Taylor,
M Thompson,
S V Faraone,
P Asherson
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ABSTRACT: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, starting in early childhood and persisting into adulthood in the majority of cases. Family and twin studies have demonstrated the importance of genetic factors and candidate gene association studies have identified several loci that exert small but significant effects on ADHD. To provide further clarification of reported associations and identify novel associated genes, we examined 1,038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes involved in the regulation of neurotransmitter pathways, particularly dopamine, norepinephrine and serotonin pathways, in addition to circadian rhythm genes. Analysis used within family tests of association in a sample of 776 DSM-IV ADHD combined type cases ascertained for the International Multi-centre ADHD Gene project. We found nominal significance with one or more SNPs in 18 genes, including the two most replicated findings in the literature: DRD4 and DAT1. Gene-wide tests, adjusted for the number of SNPs analysed in each gene, identified associations with TPH2, ARRB2, SYP, DAT1, ADRB2, HES1, MAOA and PNMT. Further studies will be needed to confirm or refute the observed associations and their generalisability to other samples.
Molecular Psychiatry 11/2006; 11(10):934-53. · 13.67 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Bovine mammillitis virus (BMV) cross-reacted in neutralization and radioimmune assay with herpes simplex virus (HSV) and pre-immunization with BMV protected against challenge by type 2 HSV. There was no evidence to suggest a pathogenic role for BMV as adjudged by a literature search or field enquiry and BMV specific antibody was not detected in 21 human sera or in four sera from personnel engaged in research with BMV; in addition there was no replication or antigen synthesis by BMV in explants of human tissue or cell lines of human origin. It is proposed that BMV might provide an alternative vaccine against HSV infections of human subjects.
Vaccine.
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K Zhou,
P Asherson,
P Sham,
B Franke,
R J L Anney,
J Buitelaar,
R Ebstein,
M Gill, K Brookes,
C Buschgens, [......],
I Manor,
A Miranda,
R D Oades,
H Roeyers,
A Rothenberger,
J Sergeant,
H C Steinhausen,
E Taylor,
M Thompson,
S V Faraone
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Limited success has been achieved through previous attention-deficit/hyperactivity disorder (ADHD) linkage scans, which were all designed to map genes underlying the dichotomous phenotype. The International Multi-centre ADHD Genetics (IMAGE) project performed a whole genome linkage scan specifically designed to map ADHD quantitative trait loci (QTL). METHODS: A set of 1094 single selected Caucasian ADHD nuclear families was genotyped on a highly accurate and informative single nucleotide polymorphism (SNP) panel. Two quantitative traits measuring the children's symptoms in home and school settings were collected and standardized according to a population sample of 8000 children to reflect the developmental nature and gender prevalence difference of ADHD. Univariate linkage test was performed on both traits and their mean score. RESULTS: A significant common linkage locus was found at chromosome 1p36 with a locus-specific heritability of 5.1% and a genomewide empirical p < .04. Setting-specific suggestive linkage signals were also found: logarithm of odds (LOD) = 2.2 at 9p23 for home trait and LOD = 2.6 at 11q21 for school trait. CONCLUSIONS: These results indicate that given large samples with proper phenotypic measures, searching for ADHD genes with a QTL strategy is an important alternative to using the clinical diagnosis. The fact that our linkage region 1p36 overlaps with the dyslexia QTL DYX8 further suggests it is potentially a pleiotropic locus for ADHD and dyslexia.
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X Xu,
E A Duman,
R Anney, K Brookes,
B Franke,
K Zhou,
C Buschgens,
W Chen,
H Christiansen,
J Eisenberg, [......],
F Mulas,
R D Oades,
H Roeyers,
A Rothenberger,
J Sergeant,
E Sonuga-Barke,
H C Steinhausen,
E Taylor,
S V Faraone,
P Asherson
