title: Sapap3 and pathological grooming in humans: Results from the OCD collaborative genetics study.
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 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.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. jbienven@jhmi.edu
authors.forename: O J
authors.initials: OJ
authors.lastname: Bienvenu
authors.forename: Y
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authors.lastname: Wang
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authors.initials: YY
authors.lastname: Shugart
authors.forename: J M
authors.initials: JM
authors.lastname: Welch
authors.forename: M A
authors.initials: MA
authors.lastname: Grados
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authors.initials: AJ
authors.lastname: Fyer
authors.forename: S L
authors.initials: SL
authors.lastname: Rauch
authors.forename: J T
authors.initials: JT
authors.lastname: McCracken
authors.forename: S A
authors.initials: SA
authors.lastname: Rasmussen
authors.forename: D L
authors.initials: DL
authors.lastname: Murphy
authors.forename: B
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authors.lastname: Cullen
authors.forename: D
authors.initials: D
authors.lastname: Valle
authors.forename: R
authors.initials: R
authors.lastname: Hoehn-Saric
authors.forename: B D
authors.initials: BD
authors.lastname: Greenberg
authors.forename: A
authors.initials: A
authors.lastname: Pinto
authors.forename: J A
authors.initials: JA
authors.lastname: Knowles
authors.forename: J
authors.initials: J
authors.lastname: Piacentini
authors.forename: D L
authors.initials: DL
authors.lastname: Pauls
authors.forename: K Y
authors.initials: KY
authors.lastname: Liang
authors.forename: V L
authors.initials: VL
authors.lastname: Willour
authors.forename: M
authors.initials: M
authors.lastname: Riddle
authors.forename: J F
authors.initials: JF
authors.lastname: Samuels
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authors.lastname: Feng
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mesh_terms: D000293:Adolescent; D002648:Child; D003299:Cooperative Behavior; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D006239:Haplotypes; D006801:Humans; D006920:Hygiene; D015810:Linkage Disequilibrium; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009771:Obsessive-Compulsive Disorder / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D000074407:SAP90-PSD95 Associated Proteins
chemical_list: C543515:DLGAP3 protein, human; D009419:Nerve Tissue Proteins; D000074407:SAP90-PSD95 Associated Proteins