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Sapap3 and pathological grooming in humans: Results from the OCD collaborative genetics study
Open accessAbstract
SAP 90/PSD95‐a ssociated p rotein (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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“The potential relevance of SAPAP3, in particular, to trichotillomania, is reinforced by the finding that rare variations in the SAPAP3 gene are associated with human disorders such as hair pulling.[23]”
From Trichotillomania (hair pulling disorder) (2019) · cites this paper as [23]
In the citing paper
“a recent human genetics study found no association of SAPAP3 single nucleotide polymorphisms with OCD, but did find associations with grooming disorders such as pathologic skin picking, trichotillomania, and/or nail biting 94.”
From DISSECTING OCD CIRCUITS: FROM ANIMAL MODELS TO TARGETED TREATMENTS: Review: Dissecting OCD Circuits: Animals to Treatments (2015) · cites this paper as [94]
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“Particularly pathological body care such as nail biting seems to be associated with SAPAP3 mutations [8].”
From Projection-specific deficits in synaptic transmission in adult Sapap3-knockout mice (2020) · cites this paper as [8]
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Self-citation
Metadata
- Authors
- 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.
- Affiliations
- Johns Hopkins University (US)
- Duke Medical Center (US)
- New York State Psychiatric Institute (US)
- Harvard University (US)
- University of California, Los Angeles (US)
- Butler Hospital (US)
- National Institutes of Health (US)
- Corresponding author
- Bienvenu, O.J.
- ORCID
- Venue
- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
- Publisher
- Wiley
- Published
- 2009-06-15
- Volume
- 150B
- Issue
- 5
- Pages
- 710-720
- ISSN
- 1552-4841 (ISSN-L)
- 1552-485X
- PMC
- PMC10885776
- OpenAlex
- W1992922886
- Cited by
- 207
- References
- 62
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 12 · 2023: 9 · 2022: 9 · 2021: 12 · 2020: 15 · 2019: 16 · 2018: 9 · 2017: 10 · 2016: 17 · 2015: 15 · 2014: 21 · 2013: 7 · 2012: 14
- FWCI
- 10.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Ontario Council on Graduate Studies, Council of Ontario Universities
- National Institutes of Health (5k23mh066284-03, MH50125, MH66284, RR-00052)
- National Institute of Mental Health (MH64543, R01MH050214, K23MH064543, MH66284, K23-MH066284, R01MH079487, MH50125)
- National Institute of Neurological Disorders and Stroke (R01NS042609, NS42609)
- National Center for Research Resources (RR 000 52, M01RR000052)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- obsessive-compulsive disorder, trichotillomania, skin picking, nail biting, postsynaptic density, candidate genes, single nucleotide polymorphisms, haplotypes, family-based association, genetic susceptibility
- MeSH terms
- SAP90-PSD95 Associated Proteins, Adolescent, Child, Cooperative Behavior, DNA Mutational Analysis, Family, Female, Gene Frequency, Genetics, Population, Haplotypes, Humans, Hygiene, Male, Nerve Tissue Proteins, Obsessive-Compulsive Disorder, Linkage Disequilibrium, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide
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