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Bienvenu, O.J.; Wang, Y.; Shugart, Y.Y.; Welch, J.M.; Grados, M.A.; Fyer, A.J.; Rauch, S.L.; McCracken, J.T.; Rasmussen, S.A.; Murphy, D.L.; Cullen, B.; Valle, D.; Hoehn-Saric, R.; Greenberg, B.D.; Pinto, A.; Knowles, J.A.; Piacentini, J.; Pauls, D.L.; Liang, K.Y.; Willour, V.L.; Riddle, M.; Samuels, J.F.; Feng, G.; Nestadt, G.
American journal of medical genetics. Part B, Neuropsychiatric genetics, 5 July 2009, Volume: 150B, Issue: 5Journal Article
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 cortico‐striatal 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 to confirm this preliminary evidence of association. © 2008 Wiley‐Liss, Inc.
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