Abstract
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.
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Acknowledgements
This research was funded by a Medical Research Council (MRC) component grant to the Social Genetic Developmental Psychiatry Research Centre. Jonathan Mill is an MRC PhD student. We thank Dr Margaret Thompson, Dr Ann York, Dr Quentin Spender, Dr Saama El Abd, Dr Mark Berlowitz, Dr Fiona McNicholas, Dr Mary Cameron, Jonathan Sharp, Claire Batten, and Shamira Fernando for their assistance in recruiting the clinical sample.
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Mill, J., Richards, S., Knight, J. et al. Haplotype analysis of SNAP-25 suggests a role in the aetiology of ADHD. Mol Psychiatry 9, 801–810 (2004). https://doi.org/10.1038/sj.mp.4001482
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DOI: https://doi.org/10.1038/sj.mp.4001482
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