Abstract
SAP90/PSD95-associated protein (SAPAP) family proteins are post-synaptic density (PSD) components that interact with other proteins to form a key scaffolding complex at excitatory (glutamatergic) synapses. A recent study found that mice with a deletion of the Sapap3 gene groomed themselves excessively, exhibited increased anxiety-like behaviors, and had corticostriatal synaptic defects, all of which were preventable with lentiviral-mediated expression of Sapap3 in the striatum; the behavioral abnormalities were also reversible with fluoxetine. In the current study, we sought to determine whether variation within the human Sapap3 gene was associated with grooming disorders (GDs: pathologic nail biting, pathologic skin picking, and/or trichotillomania) and/or obsessive-compulsive disorder (OCD) in 383 families thoroughly phenotyped for OCD genetic studies. We conducted family-based association analyses using the FBAT and GenAssoc statistical packages. Thirty-two percent of the 1,618 participants met criteria for a GD, and 65% met criteria for OCD. Four of six SNPs were nominally associated (P<0.05) with at least one GD (genotypic relative risks: 1.6-3.3), and all three haplotypes were nominally associated with at least one GD (permuted P<0.05). None of the SNPs or haplotypes were significantly associated with OCD itself. We conclude that Sapap3 is a promising functional candidate gene for human GDs, though further work is necessary toconfirm this preliminary evidence of association.
Original language | English (US) |
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Pages (from-to) | 710-720 |
Number of pages | 11 |
Journal | American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics |
Volume | 150 |
Issue number | 5 |
DOIs | |
State | Published - Jul 5 2009 |
Keywords
- Dlgap3
- Genes
- Nail biting
- Obsessive-compulsive disorder
- Trichotillomania
ASJC Scopus subject areas
- Genetics(clinical)
- Psychiatry and Mental health
- Cellular and Molecular Neuroscience