Association of a Polyadenylation Polymorphism in the Serotonin Transporter and Panic Disorder
Background Genetic markers in the serotonin transporter are associated with panic disorder (PD). The associated polymorphisms do not include the serotonin transporter-linked polymorphic region and display no obvious functional attributes. A common polymorphism (rs3813034) occurs in one of the two re...
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| Veröffentlicht in: | Biological psychiatry (1969) 2010-02, Vol.67 (4), p.331-338 |
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| creator | Gyawali, Sandeep Subaran, Ryan Weissman, Myrna M Hershkowitz, Dylan McKenna, Morgan C Talati, Ardesheer Fyer, Abby J Wickramaratne, Priya Adams, Phillip B Hodge, Susan E Schmidt, Carl J Bannon, Michael J Glatt, Charles E |
| description | Background Genetic markers in the serotonin transporter are associated with panic disorder (PD). The associated polymorphisms do not include the serotonin transporter-linked polymorphic region and display no obvious functional attributes. A common polymorphism (rs3813034) occurs in one of the two reported polyadenylation signals for the serotonin transporter and is in linkage disequilibrium with the PD-associated markers. If functional, rs3813034 might be the risk factor that explains the association of the serotonin transporter and PD. Methods Quantitative polymerase chain reaction on human brain samples ( n = 65) and lymphoblast cultures ( n = 71) was used to test rs3813034 for effects on expression of the polyadenylation forms of the serotonin transporter. rs3813034 was also tested for association in a sample of PD cases ( n = 307) and a control sample ( n = 542) that has similar population structure. Results The balance of the two polyadenylation forms of the serotonin transporter is associated with rs3813034 in brain ( p < .001) and lymphoblasts ( p < .001). The balance of the polyadenylation forms is also associated with gender in brain only ( p < .05). Association testing of rs3813034 in PD identified a significant association ( p = .0068) with a relative risk of 1.56 and 1.81 for the heterozygous and homozygous variant genotypes, respectively. Conclusions rs3813034 is a functional polymorphism in the serotonin transporter that alters the balance of the two polyadenylation forms of the serotonin transporter. rs3813034 is a putative risk factor for PD and other behavioral disorders that involve dysregulation of serotonergic neurotransmission. |
| doi_str_mv | 10.1016/j.biopsych.2009.10.015 |
| format | Article |
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The associated polymorphisms do not include the serotonin transporter-linked polymorphic region and display no obvious functional attributes. A common polymorphism (rs3813034) occurs in one of the two reported polyadenylation signals for the serotonin transporter and is in linkage disequilibrium with the PD-associated markers. If functional, rs3813034 might be the risk factor that explains the association of the serotonin transporter and PD. Methods Quantitative polymerase chain reaction on human brain samples ( n = 65) and lymphoblast cultures ( n = 71) was used to test rs3813034 for effects on expression of the polyadenylation forms of the serotonin transporter. rs3813034 was also tested for association in a sample of PD cases ( n = 307) and a control sample ( n = 542) that has similar population structure. Results The balance of the two polyadenylation forms of the serotonin transporter is associated with rs3813034 in brain ( p < .001) and lymphoblasts ( p < .001). The balance of the polyadenylation forms is also associated with gender in brain only ( p < .05). Association testing of rs3813034 in PD identified a significant association ( p = .0068) with a relative risk of 1.56 and 1.81 for the heterozygous and homozygous variant genotypes, respectively. Conclusions rs3813034 is a functional polymorphism in the serotonin transporter that alters the balance of the two polyadenylation forms of the serotonin transporter. rs3813034 is a putative risk factor for PD and other behavioral disorders that involve dysregulation of serotonergic neurotransmission.</description><identifier>ISSN: 0006-3223</identifier><identifier>EISSN: 1873-2402</identifier><identifier>DOI: 10.1016/j.biopsych.2009.10.015</identifier><identifier>PMID: 19969287</identifier><identifier>CODEN: BIPCBF</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adult and adolescent clinical studies ; Animals ; Anxiety disorders. Neuroses ; Biological and medical sciences ; Brain - metabolism ; Chi-Square Distribution ; Female ; Gender ; Gene Frequency ; genetic ; Genome-Wide Association Study - methods ; Genotype ; Humans ; Linkage Disequilibrium ; Lymphocytes - metabolism ; Male ; Medical sciences ; Mice ; Panic disorder ; Panic Disorder - genetics ; Panic Disorder - pathology ; polyadenylation ; Polyadenylation - genetics ; polymorphism ; Polymorphism, Genetic - genetics ; Psychiatry ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Serotonin Plasma Membrane Transport Proteins - genetics ; serotonin transporter ; Sex Factors ; Statistics as Topic</subject><ispartof>Biological psychiatry (1969), 2010-02, Vol.67 (4), p.331-338</ispartof><rights>Society of Biological Psychiatry</rights><rights>2010 Society of Biological Psychiatry</rights><rights>2015 INIST-CNRS</rights><rights>2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c621t-93f1f77c5c60eee2f4e2dcb21508b9485f52defc1fbb7f695959954164318e403</citedby><cites>FETCH-LOGICAL-c621t-93f1f77c5c60eee2f4e2dcb21508b9485f52defc1fbb7f695959954164318e403</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006322309012335$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22362571$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19969287$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gyawali, Sandeep</creatorcontrib><creatorcontrib>Subaran, Ryan</creatorcontrib><creatorcontrib>Weissman, Myrna M</creatorcontrib><creatorcontrib>Hershkowitz, Dylan</creatorcontrib><creatorcontrib>McKenna, Morgan C</creatorcontrib><creatorcontrib>Talati, Ardesheer</creatorcontrib><creatorcontrib>Fyer, Abby J</creatorcontrib><creatorcontrib>Wickramaratne, Priya</creatorcontrib><creatorcontrib>Adams, Phillip B</creatorcontrib><creatorcontrib>Hodge, Susan E</creatorcontrib><creatorcontrib>Schmidt, Carl J</creatorcontrib><creatorcontrib>Bannon, Michael J</creatorcontrib><creatorcontrib>Glatt, Charles E</creatorcontrib><title>Association of a Polyadenylation Polymorphism in the Serotonin Transporter and Panic Disorder</title><title>Biological psychiatry (1969)</title><addtitle>Biol Psychiatry</addtitle><description>Background Genetic markers in the serotonin transporter are associated with panic disorder (PD). The associated polymorphisms do not include the serotonin transporter-linked polymorphic region and display no obvious functional attributes. A common polymorphism (rs3813034) occurs in one of the two reported polyadenylation signals for the serotonin transporter and is in linkage disequilibrium with the PD-associated markers. If functional, rs3813034 might be the risk factor that explains the association of the serotonin transporter and PD. Methods Quantitative polymerase chain reaction on human brain samples ( n = 65) and lymphoblast cultures ( n = 71) was used to test rs3813034 for effects on expression of the polyadenylation forms of the serotonin transporter. rs3813034 was also tested for association in a sample of PD cases ( n = 307) and a control sample ( n = 542) that has similar population structure. Results The balance of the two polyadenylation forms of the serotonin transporter is associated with rs3813034 in brain ( p < .001) and lymphoblasts ( p < .001). The balance of the polyadenylation forms is also associated with gender in brain only ( p < .05). Association testing of rs3813034 in PD identified a significant association ( p = .0068) with a relative risk of 1.56 and 1.81 for the heterozygous and homozygous variant genotypes, respectively. Conclusions rs3813034 is a functional polymorphism in the serotonin transporter that alters the balance of the two polyadenylation forms of the serotonin transporter. rs3813034 is a putative risk factor for PD and other behavioral disorders that involve dysregulation of serotonergic neurotransmission.</description><subject>Adult and adolescent clinical studies</subject><subject>Animals</subject><subject>Anxiety disorders. Neuroses</subject><subject>Biological and medical sciences</subject><subject>Brain - metabolism</subject><subject>Chi-Square Distribution</subject><subject>Female</subject><subject>Gender</subject><subject>Gene Frequency</subject><subject>genetic</subject><subject>Genome-Wide Association Study - methods</subject><subject>Genotype</subject><subject>Humans</subject><subject>Linkage Disequilibrium</subject><subject>Lymphocytes - metabolism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Panic disorder</subject><subject>Panic Disorder - genetics</subject><subject>Panic Disorder - pathology</subject><subject>polyadenylation</subject><subject>Polyadenylation - genetics</subject><subject>polymorphism</subject><subject>Polymorphism, Genetic - genetics</subject><subject>Psychiatry</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>Serotonin Plasma Membrane Transport Proteins - genetics</subject><subject>serotonin transporter</subject><subject>Sex Factors</subject><subject>Statistics as Topic</subject><issn>0006-3223</issn><issn>1873-2402</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk1v1DAQhi0EotvCX6hyQZyy-CNfvlRUBUqlSq3UckSW44xZL4kdPNlK-fc42qUULpUP1ozfeT2aZwg5ZXTNKKs-bNetCyPOZrPmlMqUXFNWviAr1tQi5wXlL8mKUlrlgnNxRI4RtymsOWevyRGTspK8qVfk-zliME5PLvgs2Exnt6GfdQd-7vfJJR5CHDcOh8z5bNpAdgcxTMGn6D5qj2OIE8RM-y671d6Z7JPDEDuIb8grq3uEt4f7hHz78vn-4mt-fXN5dXF-nZuKsymXwjJb16Y0FQUAbgvgnWk5K2nTyqIpbck7sIbZtq1tJct0ZFmwqhCsgYKKE3K29x137QCdAT9F3asxukHHWQXt1L8v3m3Uj_CguGyoKJpk8P5gEMOvHeCkBocG-l57CDtUtRBNwwUTSVntlSYGxAj28RdG1YJGbdUfNGpBs-QTmlR4-rTHv2UHFknw7iDQaHRv02SNw0ddwljxsmZJ93GvgzTRBwdRoXHgDXQugplUF9zzvZz9Z2F6l8Dp_ifMgNuwiz7xUkwhV1TdLYu07BGVlHEhSvEb013Hgw</recordid><startdate>20100215</startdate><enddate>20100215</enddate><creator>Gyawali, Sandeep</creator><creator>Subaran, Ryan</creator><creator>Weissman, Myrna M</creator><creator>Hershkowitz, Dylan</creator><creator>McKenna, Morgan C</creator><creator>Talati, Ardesheer</creator><creator>Fyer, Abby J</creator><creator>Wickramaratne, Priya</creator><creator>Adams, Phillip B</creator><creator>Hodge, Susan E</creator><creator>Schmidt, Carl J</creator><creator>Bannon, Michael J</creator><creator>Glatt, Charles E</creator><general>Elsevier Inc</general><general>Elsevier</general><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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20100215</creationdate><title>Association of a Polyadenylation Polymorphism in the Serotonin Transporter and Panic Disorder</title><author>Gyawali, Sandeep ; Subaran, Ryan ; Weissman, Myrna M ; Hershkowitz, Dylan ; McKenna, Morgan C ; Talati, Ardesheer ; Fyer, Abby J ; Wickramaratne, Priya ; Adams, Phillip B ; Hodge, Susan E ; Schmidt, Carl J ; Bannon, Michael J ; Glatt, Charles E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c621t-93f1f77c5c60eee2f4e2dcb21508b9485f52defc1fbb7f695959954164318e403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adult and adolescent clinical studies</topic><topic>Animals</topic><topic>Anxiety disorders. Neuroses</topic><topic>Biological and medical sciences</topic><topic>Brain - metabolism</topic><topic>Chi-Square Distribution</topic><topic>Female</topic><topic>Gender</topic><topic>Gene Frequency</topic><topic>genetic</topic><topic>Genome-Wide Association Study - methods</topic><topic>Genotype</topic><topic>Humans</topic><topic>Linkage Disequilibrium</topic><topic>Lymphocytes - metabolism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Panic disorder</topic><topic>Panic Disorder - genetics</topic><topic>Panic Disorder - pathology</topic><topic>polyadenylation</topic><topic>Polyadenylation - genetics</topic><topic>polymorphism</topic><topic>Polymorphism, Genetic - genetics</topic><topic>Psychiatry</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. Psychiatry</topic><topic>Serotonin Plasma Membrane Transport Proteins - genetics</topic><topic>serotonin transporter</topic><topic>Sex Factors</topic><topic>Statistics as Topic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gyawali, Sandeep</creatorcontrib><creatorcontrib>Subaran, Ryan</creatorcontrib><creatorcontrib>Weissman, Myrna M</creatorcontrib><creatorcontrib>Hershkowitz, Dylan</creatorcontrib><creatorcontrib>McKenna, Morgan C</creatorcontrib><creatorcontrib>Talati, Ardesheer</creatorcontrib><creatorcontrib>Fyer, Abby J</creatorcontrib><creatorcontrib>Wickramaratne, Priya</creatorcontrib><creatorcontrib>Adams, Phillip B</creatorcontrib><creatorcontrib>Hodge, Susan E</creatorcontrib><creatorcontrib>Schmidt, Carl J</creatorcontrib><creatorcontrib>Bannon, Michael J</creatorcontrib><creatorcontrib>Glatt, Charles E</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biological psychiatry (1969)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gyawali, Sandeep</au><au>Subaran, Ryan</au><au>Weissman, Myrna M</au><au>Hershkowitz, Dylan</au><au>McKenna, Morgan C</au><au>Talati, Ardesheer</au><au>Fyer, Abby J</au><au>Wickramaratne, Priya</au><au>Adams, Phillip B</au><au>Hodge, Susan E</au><au>Schmidt, Carl J</au><au>Bannon, Michael J</au><au>Glatt, Charles E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of a Polyadenylation Polymorphism in the Serotonin Transporter and Panic Disorder</atitle><jtitle>Biological psychiatry (1969)</jtitle><addtitle>Biol Psychiatry</addtitle><date>2010-02-15</date><risdate>2010</risdate><volume>67</volume><issue>4</issue><spage>331</spage><epage>338</epage><pages>331-338</pages><issn>0006-3223</issn><eissn>1873-2402</eissn><coden>BIPCBF</coden><abstract>Background Genetic markers in the serotonin transporter are associated with panic disorder (PD). The associated polymorphisms do not include the serotonin transporter-linked polymorphic region and display no obvious functional attributes. A common polymorphism (rs3813034) occurs in one of the two reported polyadenylation signals for the serotonin transporter and is in linkage disequilibrium with the PD-associated markers. If functional, rs3813034 might be the risk factor that explains the association of the serotonin transporter and PD. Methods Quantitative polymerase chain reaction on human brain samples ( n = 65) and lymphoblast cultures ( n = 71) was used to test rs3813034 for effects on expression of the polyadenylation forms of the serotonin transporter. rs3813034 was also tested for association in a sample of PD cases ( n = 307) and a control sample ( n = 542) that has similar population structure. Results The balance of the two polyadenylation forms of the serotonin transporter is associated with rs3813034 in brain ( p < .001) and lymphoblasts ( p < .001). The balance of the polyadenylation forms is also associated with gender in brain only ( p < .05). Association testing of rs3813034 in PD identified a significant association ( p = .0068) with a relative risk of 1.56 and 1.81 for the heterozygous and homozygous variant genotypes, respectively. Conclusions rs3813034 is a functional polymorphism in the serotonin transporter that alters the balance of the two polyadenylation forms of the serotonin transporter. rs3813034 is a putative risk factor for PD and other behavioral disorders that involve dysregulation of serotonergic neurotransmission.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>19969287</pmid><doi>10.1016/j.biopsych.2009.10.015</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult and adolescent clinical studies Animals Anxiety disorders. Neuroses Biological and medical sciences Brain - metabolism Chi-Square Distribution Female Gender Gene Frequency genetic Genome-Wide Association Study - methods Genotype Humans Linkage Disequilibrium Lymphocytes - metabolism Male Medical sciences Mice Panic disorder Panic Disorder - genetics Panic Disorder - pathology polyadenylation Polyadenylation - genetics polymorphism Polymorphism, Genetic - genetics Psychiatry Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Serotonin Plasma Membrane Transport Proteins - genetics serotonin transporter Sex Factors Statistics as Topic |
| title | Association of a Polyadenylation Polymorphism in the Serotonin Transporter and Panic Disorder |
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