5 results on '"O'Donovan, Michael"'
Search Results
2. Advances in genetic findings on attention deficit hyperactivity disorder.
- Author
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Thapar, Anita, Langley, Kate, Owen, Michael J., and O'Donovan, Michael C.
- Subjects
ATTENTION-deficit hyperactivity disorder ,BEHAVIOR disorders in children ,DOPAMINE ,GENES ,ETIOLOGY of diseases - Abstract
ABSTRACTAttention deficit hyperactivity disorder (ADHD) is a common, childhood-onset neurodevelopmental disorder with adverse consequences during adult life. Family, twin and adoption studies show that genetic factors contribute to the aetiology of ADHD and that environmental factors also play a role. Family and twin studies have shown the importance of genetic influences on continuity in ADHD over time and in accounting for the co-occurrence of ADHD and conduct disorder problems. In meta-analyses of molecular genetic studies, the 48-bp variable number tandem repeat (VNTR) variant in the dopamine D4 gene and the CA(n) microsatellite marker in the D5 receptor gene have been found to be repeatedly associated with ADHD. Results from meta-analyses of the 480-bp VNTR in the dopamine transporter gene are mixed. Several genetic studies have also identified genetic variants that are related to specific clinical and developmental features of ADHD. In the next few years, a new generation of much larger-scale genetic studies should lead to the identification of further ADHD susceptibility genes. Such studies will also need to be integrated with other areas of neuroscience, clinical and epidemiological research to investigate how specific gene variants exert risk effects, interact with environmental factors and enable identification of the underlying causal mechanisms that lead to ADHD. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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3. Association of the dopamine D4 receptor gene 7-repeat allele with neuropsychological test performance of children with ADHD.
- Author
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Langley, Kate, Marshall, Lucy, Bree, Marianne van den, Thomas, Hollie, Owen, Michael, O'donovan, Michael, Thapar, Anita, and van den Bree, Marianne
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ATTENTION-deficit hyperactivity disorder ,NEUROPSYCHOLOGICAL tests ,HYPERACTIVE children ,IMPULSE control disorders in children ,DOPAMINE ,GENES - Abstract
Objective: Association between attention deficit hyperactivity disorder (ADHD) and the 7-repeat allele of a variant (a 48 bp variable number of tandem repeats) in the dopamine D4 receptor gene (DRD4) has been widely documented. A meta-analysis of 21 studies revealed evidence of significant association. In this article the authors examine whether the DRD4 7-repeat allele is associated with performance on a variety of neuropsychological tasks in children with ADHD.Method: The presence or absence of the 7-repeat allele was determined in 133 drug-naive children 6 to 13 years of age who fulfilled diagnostic criteria for ADHD. These children were then assessed on several neuropsychological tests known to be associated with attention, impulse control, and response inhibition (the Continuous Performance Test, Matching Familiar Figures Test, Go/No Go Task, and Stop Task). Activity levels were assessed with an actigraph. Children with and without at least one 7-repeat allele were compared with each other and with children in a previous population-based study.Results: Children who had the 7-repeat allele had significantly more incorrect responses on the Matching Familiar Figures Test (16.1 versus 14.3) than children who did not have the allele. Children with the allele also had shorter mean reaction times for incorrect responses on the Matching Familiar Figures Test (846.1 versus 1103.7 msec) and on the Stop Task (116.6 versus 134.1 msec) than children without the allele. Children with the allele also displayed higher activity levels. The children with and without the allele did not differ significantly in number of ADHD symptoms when the symptoms were split into the areas of inattention and hyperactivity/impulsivity. Both groups of children with ADHD were more neuropsychologically impaired than the nonpatient comparison group.Conclusions: In children with ADHD, possession of the DRD4 7-repeat allele appears to be associated with an inaccurate, impulsive response style on neuropsychological tasks that is not explained by ADHD symptom severity. [ABSTRACT FROM AUTHOR]- Published
- 2004
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4. Genome-Wide Analysis of Copy Number Variants in Attention Deficit Hyperactivity Disorder: The Role of Rare Variants and Duplications at 15q13.3.
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Williams, Nigel M., Franke, Barbara, Mick, Eric, Anney, Richard J. L., Freitag, Christine M., Gill, Michael, Thapar, Anita, O'Donovan, Michael C., Owen, Michael J., Holmans, Peter, Kent, Lindsey, Middleton, Frank, Yanli Zhang-James, Lu Liu, Meyer, Jobst, Thuy Trang Nguyen, Romanos, Jasmin, Romanos, Marcel, Seitz, Christiane, and Renner, Tobias J.
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ATTENTION-deficit hyperactivity disorder ,GENOMES ,CHROMOSOMES ,GENES - Abstract
Objective: Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable psychiatric disorder. Because of its multifactorial etiology, however, identifying the genes involved has been difficult. The authors followed up on recent findings suggesting that rare copy number variants (CNVs) may be important for ADHD etiology. Method: The authors performed a genome-wide analysis of large, rare CNVs (<1% population frequency) in children with ADHD (N=896) and comparison subjects (N=2,455) from the IMAGE II Consortium. Results: The authors observed 1,562 individually rare CNVs >100 kb in size, which segregated into 912 independent loci. Overall, the rate of rare CNVs >100 kb was 1.15 times higher in ADHD case subjects relative to comparison subjects, with duplications spanning known genes showing a 1.2-fold enrichment. In accordance with a previous study, rare CNVs >500 kb showed the greatest enrichment (1.28-fold). CNVs identified in ADHD case subjects were significantly enriched for loci implicated in autism and in schizophrenia. Duplications spanning the CHRNA7 gene at chromosome 15q13.3 were associated with ADHD in single-locus analysis. This finding was consistently replicated in an additional 2,242 ADHD case subjects and 8,552 comparison subjects from four independent cohorts from the United Kingdom, the United States, and Canada. Presence of the duplication at 15q13.3 appeared to be associated with comorbid conduct disorder. Conclusions: These findings support the enrichment of large, rare CNVs in ADHD and implicate duplications at 15q13.3 as a novel risk factor for ADHD. With a frequency of 0.6% in the populations investigated and a relatively large effect size (odds ratio=2.22, 95% confidence interval=1.5-3.6), this locus could be an important contributor to ADHD etiology. [ABSTRACT FROM AUTHOR]
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- 2012
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5. A Family Based Study Implicates Solute Carrier Family 1–Member 3 (SLC1A3) Gene in Attention-Deficit/Hyperactivity Disorder
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Turic, Darko, Langley, Kate, Williams, Hywel, Norton, Nadine, Williams, Nigel M., Moskvina, Valentina, Van den Bree, Marianne B., Owen, Michael J., Thapar, Anita, and O’Donovan, Michael C.
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NEUROTRANSMITTERS , *CENTRAL nervous system , *ATTENTION-deficit hyperactivity disorder , *NEUROPSYCHOLOGY , *GENES , *GENETICS - Abstract
Background: The glutamatergic system, the major excitatory neurotransmitter system in the central nervous system (CNS) has been proposed as contributing a possible role in the etiology of attention deficit hyperactivity disorder (ADHD). This is based upon observations from animal, neuroimaging, neuroanatomical and neuropsychological studies. Genes related to glutamate function are therefore good functional candidates for this disorder. The SLC1A3 (Solute Carrier Family 1, member 3) gene encodes a glial glutamate transporter which maps to chromosome 5p12, a region of linkage that coincides in two published ADHD genome scans so far. SLC1A3 is thus both a functional and positional candidate gene for ADHD. Methods: We have undertaken detailed association analysis of SLC1A3 using a multi-stage approach for candidate gene analysis. Results: In a family-based sample (n = 299) we found a significant association between marker rs2269272 (p = .007) and ADHD. Two, two-marker haplotypes, rs2269272/rs3776581 (p = .016) and rs2269272/rs2032893 (p = .013) also yielded evidence of association. Conclusions: The results of our study suggest that genetic variation in SLC1A3 may contribute to susceptibility to ADHD. [Copyright &y& Elsevier]
- Published
- 2005
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