G2Cdb::Human Disease report

Disease id
D00000179
Name
Attention deficit hyperactivity disorder
Nervous system disease
yes

Genes (2)

Gene Name/Description Mutations Found Literature Mutations Type Genetic association?
G00000026 GRIN2A
glutamate receptor, ionotropic, N-methyl D-aspartate 2A
Y (14966475) Single nucleotide polymorphism (SNP) Y
G00002531 SNAP25
synaptosomal-associated protein, 25kDa
Y (17325713) Single nucleotide polymorphism (SNP) ?
G00002531 SNAP25
synaptosomal-associated protein, 25kDa
Y (16088329) Polymorphism (P) ?
G00002531 SNAP25
synaptosomal-associated protein, 25kDa
Y (15007392) Single nucleotide polymorphism (SNP) Y
G00002531 SNAP25
synaptosomal-associated protein, 25kDa
Y (15007392) Microsatellite polymorphism (MSP) Y

References

  • Support for the MnlI polymorphism of SNAP25; a Korean ADHD case-control study.

    Choi TK, Lee HS, Kim JW, Park TW, Song DH, Yook KW, Lee SH, Kim JI and Suh SY

    Molecular psychiatry 2007;12;3;224-6

  • The SNAP25 gene as a susceptibility gene contributing to attention-deficit hyperactivity disorder.

    Feng Y, Crosbie J, Wigg K, Pathare T, Ickowicz A, Schachar R, Tannock R, Roberts W, Malone M, Swanson J, Kennedy JL and Barr CL

    Department of Psychiatry, Cellular and Molecular Division, The Toronto Western Research Institute, University Health Network, Toronto, ON, Canada.

    The synaptosomal-associated protein of 25 kDa gene (SNAP25) has been suggested as a genetic susceptibility factor in attention-deficit hyperactivity disorder (ADHD) based on the mouse strain coloboma. This strain is hemizygous for the SNAP25 gene and displays hyperactivity that responds to dextroamphetamine, but not to methylphenidate. Previously, we reported association of SNAP25 and ADHD using two polymorphisms. To further investigate this gene, we screened the exons for DNA variation and genotyped ten additional polymorphisms in an expanded sample of families from Toronto and a second sample of families collected in Irvine, CA. Significant results were observed in the Toronto sample for four markers, although not in the Irvine sample. The paper discusses the possible influence of the selection criteria on these differential results. The Irvine sample selected subjects that met the DSM-IV combined subtype diagnosis, whereas the Toronto sample included all subtypes. Analysis of the DSM-IV subtypes in the Toronto sample indicated that the differential results were not attributable to ADHD subtype. Differences in ethnicity, differential medication response, and other clinical characteristics of the samples cannot be ruled out at this time. Quantitative analysis of the dimensions of hyperactivity/impulsivity and inattention in the Toronto sample found that both behavioral traits were associated with SNAP25. Our findings continue to support SNAP25 in the susceptibility to ADHD.

    Funded by: NICHD NIH HHS: HD99-004; NIMH NIH HHS: U01:MH50440

    Molecular psychiatry 2005;10;11;998-1005, 973

  • Haplotype analysis of SNAP-25 suggests a role in the aetiology of ADHD.

    Mill J, Richards S, Knight J, Curran S, Taylor E and Asherson P

    Social, Genetic, and Developmental Psychiatry Research Centre, Institute of Psychiatry, Kings College, London, UK. spjgjsm@iop.kcl.ac.uk

    Several lines of evidence suggest a role for SNAP-25 (synaptosomal-associated protein of 25 kDa) in the genetic aetiology of ADHD. Most notable is the coloboma mouse mutant, which displays spontaneous hyperactivity and is hemizygous for a deletion spanning this gene. We have screened the SNAP-25 gene using denaturing high-performance liquid chromatography and sequencing, and genotyped six polymorphic single-nucleotide polymorphisms and two microsatellites in a clinically ascertained sample of 188 probands. Several markers were found to show association with ADHD, both individually and in combination with other markers to form multimarker haplotypes. Analyses of transmission by parental sex suggested that the association of SNAP-25 with ADHD is largely due to transmission of alleles from paternal chromosomes to affected probands, suggesting that this locus may be subject to genomic imprinting. Overall our data provide some evidence for a role of this gene in ADHD, although the precise causal functional variant is yet to be ascertained.

    Molecular psychiatry 2004;9;8;801-10

  • Follow-up of genetic linkage findings on chromosome 16p13: evidence of association of N-methyl-D aspartate glutamate receptor 2A gene polymorphism with ADHD.

    Turic D, Langley K, Mills S, Stephens M, Lawson D, Govan C, Williams N, Van Den Bree M, Craddock N, Kent L, Owen M, O'Donovan M and Thapar A

    Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, UK.

    Attention deficit hyperactivity disorder (ADHD) is a childhood onset disorder, for which there is good evidence that genetic factors contribute to the aetiology. Recently reported linkage findings suggested evidence of a susceptibility locus on chromosome 16p13 (maximum LOD score of 4.2, P=5 x 10(-6)). The GRIN2A (glutamate receptor, ionotropic, N-methyl D-aspartate 2A) gene that encodes the N-methyl D-aspartate receptor subunit 2A (NMDA2A) maps to this region of linkage. As this is also a good functional candidate gene for ADHD, we undertook family-based association analysis in a sample of 238 families. We found significant evidence of association with a GRIN2A exon 5 polymorphism (chi(2)=5.7, P=0.01). Our data suggest that genetic variation in GRIN2A may confer increased risk for ADHD and that this, at least in part, might be responsible for the linkage result on 16p reported by Smalley et al. We conclude that replication is required and that further work examining for association of GRIN2A polymorphisms with ADHD is warranted.

    Molecular psychiatry 2004;9;2;169-73

Literature (4)

Pubmed - other

  • Support for the MnlI polymorphism of SNAP25; a Korean ADHD case-control study.

    Choi TK, Lee HS, Kim JW, Park TW, Song DH, Yook KW, Lee SH, Kim JI and Suh SY

    Molecular psychiatry 2007;12;3;224-6

  • The SNAP25 gene as a susceptibility gene contributing to attention-deficit hyperactivity disorder.

    Feng Y, Crosbie J, Wigg K, Pathare T, Ickowicz A, Schachar R, Tannock R, Roberts W, Malone M, Swanson J, Kennedy JL and Barr CL

    Department of Psychiatry, Cellular and Molecular Division, The Toronto Western Research Institute, University Health Network, Toronto, ON, Canada.

    The synaptosomal-associated protein of 25 kDa gene (SNAP25) has been suggested as a genetic susceptibility factor in attention-deficit hyperactivity disorder (ADHD) based on the mouse strain coloboma. This strain is hemizygous for the SNAP25 gene and displays hyperactivity that responds to dextroamphetamine, but not to methylphenidate. Previously, we reported association of SNAP25 and ADHD using two polymorphisms. To further investigate this gene, we screened the exons for DNA variation and genotyped ten additional polymorphisms in an expanded sample of families from Toronto and a second sample of families collected in Irvine, CA. Significant results were observed in the Toronto sample for four markers, although not in the Irvine sample. The paper discusses the possible influence of the selection criteria on these differential results. The Irvine sample selected subjects that met the DSM-IV combined subtype diagnosis, whereas the Toronto sample included all subtypes. Analysis of the DSM-IV subtypes in the Toronto sample indicated that the differential results were not attributable to ADHD subtype. Differences in ethnicity, differential medication response, and other clinical characteristics of the samples cannot be ruled out at this time. Quantitative analysis of the dimensions of hyperactivity/impulsivity and inattention in the Toronto sample found that both behavioral traits were associated with SNAP25. Our findings continue to support SNAP25 in the susceptibility to ADHD.

    Funded by: NICHD NIH HHS: HD99-004; NIMH NIH HHS: U01:MH50440

    Molecular psychiatry 2005;10;11;998-1005, 973

  • Haplotype analysis of SNAP-25 suggests a role in the aetiology of ADHD.

    Mill J, Richards S, Knight J, Curran S, Taylor E and Asherson P

    Social, Genetic, and Developmental Psychiatry Research Centre, Institute of Psychiatry, Kings College, London, UK. spjgjsm@iop.kcl.ac.uk

    Several lines of evidence suggest a role for SNAP-25 (synaptosomal-associated protein of 25 kDa) in the genetic aetiology of ADHD. Most notable is the coloboma mouse mutant, which displays spontaneous hyperactivity and is hemizygous for a deletion spanning this gene. We have screened the SNAP-25 gene using denaturing high-performance liquid chromatography and sequencing, and genotyped six polymorphic single-nucleotide polymorphisms and two microsatellites in a clinically ascertained sample of 188 probands. Several markers were found to show association with ADHD, both individually and in combination with other markers to form multimarker haplotypes. Analyses of transmission by parental sex suggested that the association of SNAP-25 with ADHD is largely due to transmission of alleles from paternal chromosomes to affected probands, suggesting that this locus may be subject to genomic imprinting. Overall our data provide some evidence for a role of this gene in ADHD, although the precise causal functional variant is yet to be ascertained.

    Molecular psychiatry 2004;9;8;801-10

  • Follow-up of genetic linkage findings on chromosome 16p13: evidence of association of N-methyl-D aspartate glutamate receptor 2A gene polymorphism with ADHD.

    Turic D, Langley K, Mills S, Stephens M, Lawson D, Govan C, Williams N, Van Den Bree M, Craddock N, Kent L, Owen M, O'Donovan M and Thapar A

    Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, UK.

    Attention deficit hyperactivity disorder (ADHD) is a childhood onset disorder, for which there is good evidence that genetic factors contribute to the aetiology. Recently reported linkage findings suggested evidence of a susceptibility locus on chromosome 16p13 (maximum LOD score of 4.2, P=5 x 10(-6)). The GRIN2A (glutamate receptor, ionotropic, N-methyl D-aspartate 2A) gene that encodes the N-methyl D-aspartate receptor subunit 2A (NMDA2A) maps to this region of linkage. As this is also a good functional candidate gene for ADHD, we undertook family-based association analysis in a sample of 238 families. We found significant evidence of association with a GRIN2A exon 5 polymorphism (chi(2)=5.7, P=0.01). Our data suggest that genetic variation in GRIN2A may confer increased risk for ADHD and that this, at least in part, might be responsible for the linkage result on 16p reported by Smalley et al. We conclude that replication is required and that further work examining for association of GRIN2A polymorphisms with ADHD is warranted.

    Molecular psychiatry 2004;9;2;169-73

© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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