Sapap3 and pathological grooming in humans: Results from the OCD collaborative genetics study
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 excessive...
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| Veröffentlicht in: | American journal of medical genetics. Part B, Neuropsychiatric genetics Neuropsychiatric genetics, 2009-07, Vol.150B (5), p.710-720 |
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| creator | 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. |
| description | 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 |
| doi_str_mv | 10.1002/ajmg.b.30897 |
| format | Article |
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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.</description><identifier>ISSN: 1552-4841</identifier><identifier>EISSN: 1552-485X</identifier><identifier>DOI: 10.1002/ajmg.b.30897</identifier><identifier>PMID: 19051237</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adolescent ; Adult and adolescent clinical studies ; Anxiety disorders. Neuroses ; Biological and medical sciences ; Child ; Cooperative Behavior ; Dermatology ; Dlgap3 ; DNA Mutational Analysis ; Family ; Female ; Gene Frequency ; genes ; Genetic Predisposition to Disease ; Genetics, Population ; Hair and nails disorders ; Haplotypes ; Humans ; Hygiene ; Linkage Disequilibrium ; Male ; Medical genetics ; Medical sciences ; Miscellaneous ; nail biting ; Nerve Tissue Proteins - genetics ; obsessive-compulsive disorder ; Obsessive-Compulsive Disorder - genetics ; Obsessive-compulsive disorders ; Polymorphism, Single Nucleotide ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; SAP90-PSD95 Associated Proteins ; trichotillomania</subject><ispartof>American journal of medical genetics. Part B, Neuropsychiatric genetics, 2009-07, Vol.150B (5), p.710-720</ispartof><rights>Copyright © 2008 Wiley‐Liss, Inc.</rights><rights>2009 INIST-CNRS</rights><rights>2008 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5017-5749c23beafd29a7468b9ca0b67e291bd16c9e6749ea3c5a76ec051fc7a5b7b43</citedby><cites>FETCH-LOGICAL-c5017-5749c23beafd29a7468b9ca0b67e291bd16c9e6749ea3c5a76ec051fc7a5b7b43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fajmg.b.30897$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fajmg.b.30897$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21614742$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19051237$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bienvenu, O.J.</creatorcontrib><creatorcontrib>Wang, Y.</creatorcontrib><creatorcontrib>Shugart, Y.Y.</creatorcontrib><creatorcontrib>Welch, J.M.</creatorcontrib><creatorcontrib>Grados, M.A.</creatorcontrib><creatorcontrib>Fyer, A.J.</creatorcontrib><creatorcontrib>Rauch, S.L.</creatorcontrib><creatorcontrib>McCracken, J.T.</creatorcontrib><creatorcontrib>Rasmussen, S.A.</creatorcontrib><creatorcontrib>Murphy, D.L.</creatorcontrib><creatorcontrib>Cullen, B.</creatorcontrib><creatorcontrib>Valle, D.</creatorcontrib><creatorcontrib>Hoehn-Saric, R.</creatorcontrib><creatorcontrib>Greenberg, B.D.</creatorcontrib><creatorcontrib>Pinto, A.</creatorcontrib><creatorcontrib>Knowles, J.A.</creatorcontrib><creatorcontrib>Piacentini, J.</creatorcontrib><creatorcontrib>Pauls, D.L.</creatorcontrib><creatorcontrib>Liang, K.Y.</creatorcontrib><creatorcontrib>Willour, V.L.</creatorcontrib><creatorcontrib>Riddle, M.</creatorcontrib><creatorcontrib>Samuels, J.F.</creatorcontrib><creatorcontrib>Feng, G.</creatorcontrib><creatorcontrib>Nestadt, G.</creatorcontrib><title>Sapap3 and pathological grooming in humans: Results from the OCD collaborative genetics study</title><title>American journal of medical genetics. Part B, Neuropsychiatric genetics</title><addtitle>Am. J. Med. Genet</addtitle><description>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.</description><subject>Adolescent</subject><subject>Adult and adolescent clinical studies</subject><subject>Anxiety disorders. Neuroses</subject><subject>Biological and medical sciences</subject><subject>Child</subject><subject>Cooperative Behavior</subject><subject>Dermatology</subject><subject>Dlgap3</subject><subject>DNA Mutational Analysis</subject><subject>Family</subject><subject>Female</subject><subject>Gene Frequency</subject><subject>genes</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetics, Population</subject><subject>Hair and nails disorders</subject><subject>Haplotypes</subject><subject>Humans</subject><subject>Hygiene</subject><subject>Linkage Disequilibrium</subject><subject>Male</subject><subject>Medical genetics</subject><subject>Medical sciences</subject><subject>Miscellaneous</subject><subject>nail biting</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>obsessive-compulsive disorder</subject><subject>Obsessive-Compulsive Disorder - genetics</subject><subject>Obsessive-compulsive disorders</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>SAP90-PSD95 Associated Proteins</subject><subject>trichotillomania</subject><issn>1552-4841</issn><issn>1552-485X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqN0U2P0zAQBuAIgdgPuHFGvsBpU_wR2zW3pUABFVYsINBKyBo7TuoliYOdAP33pLSUG3CyD8_M2PNm2T2CZwRj-giu23pmZgzPlbyRHRPOaV7M-aebh3tBjrKTlK4xZphLeTs7IgpzQpk8zj6_gx56hqArUQ_DOjSh9hYaVMcQWt_VyHdoPbbQpcfo0qWxGRKqYmjRsHboYvEU2dA0YEKEwX9zqHadG7xNKA1jubmT3aqgSe7u_jzNPjx_9n7xIl9dLF8uzle55ZjInMtCWcqMg6qkCmQh5kZZwEZIRxUxJRFWOTEpB8xykMLZ6QOVlcCNNAU7zR7u-vYxfB1dGnTrk3XTwzoXxqSFZEoqKf4JKZ4Txaj8DyimHUo2wbMdtDGkFF2l--hbiBtNsN4GpLcBaaN_BTTx-_u-o2ld-QfvE5nAgz2ANOVQReisTwdHiSCFLOjk2M59943b_HWoPn_1evl7fL6r8mlwPw5VEL9sdyS5_vhmqS_JVUFXT670W_YTf9642Q</recordid><startdate>20090705</startdate><enddate>20090705</enddate><creator>Bienvenu, O.J.</creator><creator>Wang, Y.</creator><creator>Shugart, Y.Y.</creator><creator>Welch, J.M.</creator><creator>Grados, M.A.</creator><creator>Fyer, A.J.</creator><creator>Rauch, S.L.</creator><creator>McCracken, J.T.</creator><creator>Rasmussen, S.A.</creator><creator>Murphy, D.L.</creator><creator>Cullen, B.</creator><creator>Valle, D.</creator><creator>Hoehn-Saric, R.</creator><creator>Greenberg, B.D.</creator><creator>Pinto, A.</creator><creator>Knowles, J.A.</creator><creator>Piacentini, J.</creator><creator>Pauls, D.L.</creator><creator>Liang, K.Y.</creator><creator>Willour, V.L.</creator><creator>Riddle, M.</creator><creator>Samuels, J.F.</creator><creator>Feng, G.</creator><creator>Nestadt, G.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Liss</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20090705</creationdate><title>Sapap3 and pathological grooming in humans: Results from the OCD collaborative genetics study</title><author>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.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5017-5749c23beafd29a7468b9ca0b67e291bd16c9e6749ea3c5a76ec051fc7a5b7b43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adolescent</topic><topic>Adult and adolescent clinical studies</topic><topic>Anxiety disorders. Neuroses</topic><topic>Biological and medical sciences</topic><topic>Child</topic><topic>Cooperative Behavior</topic><topic>Dermatology</topic><topic>Dlgap3</topic><topic>DNA Mutational Analysis</topic><topic>Family</topic><topic>Female</topic><topic>Gene Frequency</topic><topic>genes</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetics, Population</topic><topic>Hair and nails disorders</topic><topic>Haplotypes</topic><topic>Humans</topic><topic>Hygiene</topic><topic>Linkage Disequilibrium</topic><topic>Male</topic><topic>Medical genetics</topic><topic>Medical sciences</topic><topic>Miscellaneous</topic><topic>nail biting</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>obsessive-compulsive disorder</topic><topic>Obsessive-Compulsive Disorder - genetics</topic><topic>Obsessive-compulsive disorders</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. 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Genet</addtitle><date>2009-07-05</date><risdate>2009</risdate><volume>150B</volume><issue>5</issue><spage>710</spage><epage>720</epage><pages>710-720</pages><issn>1552-4841</issn><eissn>1552-485X</eissn><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. © 2008 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>19051237</pmid><doi>10.1002/ajmg.b.30897</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | American journal of medical genetics. Part B, Neuropsychiatric genetics, 2009-07, Vol.150B (5), p.710-720 |
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| subjects | Adolescent Adult and adolescent clinical studies Anxiety disorders. Neuroses Biological and medical sciences Child Cooperative Behavior Dermatology Dlgap3 DNA Mutational Analysis Family Female Gene Frequency genes Genetic Predisposition to Disease Genetics, Population Hair and nails disorders Haplotypes Humans Hygiene Linkage Disequilibrium Male Medical genetics Medical sciences Miscellaneous nail biting Nerve Tissue Proteins - genetics obsessive-compulsive disorder Obsessive-Compulsive Disorder - genetics Obsessive-compulsive disorders Polymorphism, Single Nucleotide Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry SAP90-PSD95 Associated Proteins trichotillomania |
| title | Sapap3 and pathological grooming in humans: Results from the OCD collaborative genetics study |
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