Sapap3 and pathological grooming in humans: Results from the OCD collaborative genetics study

SAP90PSD95associated protein SAPAP family proteins are postsynaptic 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 Sapap3gene groomed themselves excessively, exhibited increased anxietylike behaviors, and had corticostriatal synaptic defects, all of which were preventable with lentiviralmediated expression of Sapap3in the striatum; the behavioral abnormalities were also reversible with fluoxetine. In the current study, we sought to determine whether variation within the human Sapap3gene was associated with grooming disorders GDs: pathologic nail biting, pathologic skin picking, andor trichotillomania andor obsessivecompulsive disorder OCD in 383 families thoroughly phenotyped for OCD genetic studies. We conducted familybased association analyses using the FBAT and GenAssoc statistical packages. Thirtytwo 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 Sapap3is a promising functional candidate gene for human GDs, though further work is necessary to confirm this preliminary evidence of association. © 2008 WileyLiss, Inc.