Polymorphisms in the GAD2 gene‐region are associated with susceptibility for unipolar depression and with a risk factor for anxiety disorders
Identifieur interne : 000C82 ( Istex/Corpus ); précédent : 000C81; suivant : 000C83Polymorphisms in the GAD2 gene‐region are associated with susceptibility for unipolar depression and with a risk factor for anxiety disorders
Auteurs : Paul G. Unschuld ; Marcus Ising ; Michael Specht ; Angelika Erhardt ; Stephan Ripke ; Angela Heck ; Stefan Kloiber ; Verica Straub ; Tanja Brueckl ; Bertram Müller-Myhsok ; Florian Holsboer ; Elisabeth B. BinderSource :
- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics [ 1552-4841 ] ; 2009-12-05.
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Abstract
Glutamate decarboxylase (GAD) is the rate limiting enzyme for conversion of glutamic acid to gamma‐aminobutyric acid (GABA). The GAD 65 kDa isoform is encoded by the gene GAD2 and is mainly expressed in synaptic terminals. It serves as an apoenzyme, which shows enhanced availability in situations of stress, responding to short‐term demands for GABA. We analyzed 18 single nucleotide polymorphisms (SNPs) in the GAD2‐gene region for associations with psychiatric diagnosis and behavioral inhibition (BI) derived from the personality traits neuroticism and extraversion as defined by the Eysenck Personality Questionaire (EPQ). A total of 268 patients with anxiety disorder (AD), 541 with unipolar depression (MD), and 541 healthy controls were included. We observe associations for five tag‐SNPs with BI in the AD‐ and control samples as well as two additional case–control associations in the MD‐sample. The associated SNPs lie within a 16KB linkage disequilibrium‐block, including putative 5′ GAD2‐promoter‐elements as well as the 3′ end of the gene MYO3A. Using open access mRNA‐expression data, we could show that BI‐associated SNPs appear to be associated with differences in MYO3A‐ but not GAD2 lymphoblastoid‐mRNA expression levels. These results support earlier studies that suggest associations of polymorphisms within the GAD2 locus with anxiety and affective disorders. However, data from expression studies imply that these polymorphisms could tag functional effects on the neighboring gene MYO3A, which is also expressed in the brain, including the cingulate cortex and the amygdala. © 2009 Wiley‐Liss, Inc.
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DOI: 10.1002/ajmg.b.30938
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The GAD 65 kDa isoform is encoded by the gene GAD2 and is mainly expressed in synaptic terminals. It serves as an apoenzyme, which shows enhanced availability in situations of stress, responding to short‐term demands for GABA. We analyzed 18 single nucleotide polymorphisms (SNPs) in the GAD2‐gene region for associations with psychiatric diagnosis and behavioral inhibition (BI) derived from the personality traits neuroticism and extraversion as defined by the Eysenck Personality Questionaire (EPQ). A total of 268 patients with anxiety disorder (AD), 541 with unipolar depression (MD), and 541 healthy controls were included. We observe associations for five tag‐SNPs with BI in the AD‐ and control samples as well as two additional case–control associations in the MD‐sample. The associated SNPs lie within a 16KB linkage disequilibrium‐block, including putative 5′ GAD2‐promoter‐elements as well as the 3′ end of the gene MYO3A. Using open access mRNA‐expression data, we could show that BI‐associated SNPs appear to be associated with differences in MYO3A‐ but not GAD2 lymphoblastoid‐mRNA expression levels. These results support earlier studies that suggest associations of polymorphisms within the GAD2 locus with anxiety and affective disorders. However, data from expression studies imply that these polymorphisms could tag functional effects on the neighboring gene MYO3A, which is also expressed in the brain, including the cingulate cortex and the amygdala. © 2009 Wiley‐Liss, Inc.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Paul G. 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Using open access mRNA‐expression data, we could show that BI‐associated SNPs appear to be associated with differences in MYO3A‐ but not GAD2 lymphoblastoid‐mRNA expression levels. These results support earlier studies that suggest associations of polymorphisms within the GAD2 locus with anxiety and affective disorders. 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Polymorphisms in the GAD2 Gene‐Region Are Associated With Susceptibility for Unipolar Depression and With a Risk Factor for Anxiety Disorders. Am J Med Genet Part B 150B:1100–1109.</note><note>Bavarian Ministry of Commerce</note><note>Federal Ministry of Education and Research (BMBF)</note><note>Förderkennzeichen - No. 01GS0481;</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Polymorphisms in the GAD2 gene‐region are associated with susceptibility for unipolar depression and with a risk factor for anxiety disorders</title><author xml:id="author-1"><persName><forename type="first">Paul G.</forename><surname>Unschuld</surname></persName><affiliation>Max Planck Institute of Psychiatry, München, Germany</affiliation><affiliation>Max Planck Institute of Psychiatry, Kraepelinstr. 2‐10, 80804 München, Germany.</affiliation></author><author xml:id="author-2"><persName><forename type="first">Marcus</forename><surname>Ising</surname></persName><affiliation>Max Planck Institute of Psychiatry, München, Germany</affiliation></author><author xml:id="author-3"><persName><forename type="first">Michael</forename><surname>Specht</surname></persName><affiliation>Max Planck Institute of Psychiatry, München, Germany</affiliation></author><author xml:id="author-4"><persName><forename type="first">Angelika</forename><surname>Erhardt</surname></persName><affiliation>Max Planck Institute of Psychiatry, München, Germany</affiliation></author><author xml:id="author-5"><persName><forename type="first">Stephan</forename><surname>Ripke</surname></persName><affiliation>Max Planck Institute of Psychiatry, München, Germany</affiliation></author><author xml:id="author-6"><persName><forename type="first">Angela</forename><surname>Heck</surname></persName><affiliation>Max Planck Institute of Psychiatry, München, Germany</affiliation></author><author xml:id="author-7"><persName><forename type="first">Stefan</forename><surname>Kloiber</surname></persName><affiliation>Max Planck Institute of Psychiatry, München, Germany</affiliation></author><author xml:id="author-8"><persName><forename type="first">Verica</forename><surname>Straub</surname></persName><affiliation>Max Planck Institute of Psychiatry, München, Germany</affiliation></author><author xml:id="author-9"><persName><forename type="first">Tanja</forename><surname>Brueckl</surname></persName><affiliation>Max Planck Institute of Psychiatry, München, Germany</affiliation></author><author xml:id="author-10"><persName><forename type="first">Bertram</forename><surname>Müller‐Myhsok</surname></persName><affiliation>Max Planck Institute of Psychiatry, München, Germany</affiliation></author><author xml:id="author-11"><persName><forename type="first">Florian</forename><surname>Holsboer</surname></persName><affiliation>Max Planck Institute of Psychiatry, München, Germany</affiliation></author><author xml:id="author-12"><persName><forename type="first">Elisabeth B.</forename><surname>Binder</surname></persName><affiliation>Max Planck Institute of Psychiatry, München, Germany</affiliation></author></analytic><monogr><title level="j">American Journal of Medical Genetics Part B: Neuropsychiatric Genetics</title><title level="j" type="abbrev">Am. J. Med. Genet.</title><idno type="pISSN">1552-4841</idno><idno type="eISSN">1552-485X</idno><idno type="DOI">10.1002/(ISSN)1552-485X</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2009-12-05"></date><biblScope unit="volume">150B</biblScope><biblScope unit="issue">8</biblScope><biblScope unit="page" from="1100">1100</biblScope><biblScope unit="page" to="1109">1109</biblScope></imprint></monogr><idno type="istex">50E81DE628806726E54C8C5A65DDB8796171A0D9</idno><idno type="DOI">10.1002/ajmg.b.30938</idno><idno type="ArticleID">AJMG30938</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2009</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Glutamate decarboxylase (GAD) is the rate limiting enzyme for conversion of glutamic acid to gamma‐aminobutyric acid (GABA). The GAD 65 kDa isoform is encoded by the gene GAD2 and is mainly expressed in synaptic terminals. It serves as an apoenzyme, which shows enhanced availability in situations of stress, responding to short‐term demands for GABA. We analyzed 18 single nucleotide polymorphisms (SNPs) in the GAD2‐gene region for associations with psychiatric diagnosis and behavioral inhibition (BI) derived from the personality traits neuroticism and extraversion as defined by the Eysenck Personality Questionaire (EPQ). A total of 268 patients with anxiety disorder (AD), 541 with unipolar depression (MD), and 541 healthy controls were included. We observe associations for five tag‐SNPs with BI in the AD‐ and control samples as well as two additional case–control associations in the MD‐sample. The associated SNPs lie within a 16KB linkage disequilibrium‐block, including putative 5′ GAD2‐promoter‐elements as well as the 3′ end of the gene MYO3A. Using open access mRNA‐expression data, we could show that BI‐associated SNPs appear to be associated with differences in MYO3A‐ but not GAD2 lymphoblastoid‐mRNA expression levels. These results support earlier studies that suggest associations of polymorphisms within the GAD2 locus with anxiety and affective disorders. However, data from expression studies imply that these polymorphisms could tag functional effects on the neighboring gene MYO3A, which is also expressed in the brain, including the cingulate cortex and the amygdala. © 2009 Wiley‐Liss, Inc.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>keywords</head><item><term>genetics</term></item><item><term>association</term></item><item><term>SNP</term></item><item><term>MYO3A</term></item><item><term>behavioral inhibition</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>article-category</head><item><term>Research Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2008-09-30">Received</change><change when="2009-01-14">Registration</change><change when="2009-12-05">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/50E81DE628806726E54C8C5A65DDB8796171A0D9/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>Hoboken</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1552-485X</doi><issn type="print">1552-4841</issn><issn type="electronic">1552-485X</issn><idGroup><id type="product" value="AJMG"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="AMERICAN JOURNAL OF MEDICAL GENETICS PART B: NEUROPSYCHIATRIC GENETICS">American Journal of Medical Genetics Part B: Neuropsychiatric Genetics</title><title type="short">Am. 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G.</givenNames><familyName>Unschuld</familyName></personName><contactDetails><email>unschuld@mpipsykl.mpg.de</email></contactDetails></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Marcus</givenNames><familyName>Ising</familyName></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Michael</givenNames><familyName>Specht</familyName></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Angelika</givenNames><familyName>Erhardt</familyName></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Stephan</givenNames><familyName>Ripke</familyName></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Angela</givenNames><familyName>Heck</familyName></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Stefan</givenNames><familyName>Kloiber</familyName></personName></creator><creator xml:id="au8" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Verica</givenNames><familyName>Straub</familyName></personName></creator><creator xml:id="au9" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Tanja</givenNames><familyName>Brueckl</familyName></personName></creator><creator xml:id="au10" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Bertram</givenNames><familyName>Müller‐Myhsok</familyName></personName></creator><creator xml:id="au11" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Florian</givenNames><familyName>Holsboer</familyName></personName></creator><creator xml:id="au12" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Elisabeth B.</givenNames><familyName>Binder</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="DE" type="organization"><unparsedAffiliation>Max Planck Institute of Psychiatry, München, Germany</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">genetics</keyword><keyword xml:id="kwd2">association</keyword><keyword xml:id="kwd3">SNP</keyword><keyword xml:id="kwd4">MYO3A</keyword><keyword xml:id="kwd5">behavioral inhibition</keyword></keywordGroup><fundingInfo><fundingAgency>Bavarian Ministry of Commerce</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Federal Ministry of Education and Research (BMBF)</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Förderkennzeichen</fundingAgency><fundingNumber>01GS0481</fundingNumber></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Glutamate decarboxylase (GAD) is the rate limiting enzyme for conversion of glutamic acid to gamma‐aminobutyric acid (GABA). The GAD 65 kDa isoform is encoded by the gene GAD2 and is mainly expressed in synaptic terminals. It serves as an apoenzyme, which shows enhanced availability in situations of stress, responding to short‐term demands for GABA. We analyzed 18 single nucleotide polymorphisms (SNPs) in the GAD2‐gene region for associations with psychiatric diagnosis and behavioral inhibition (BI) derived from the personality traits neuroticism and extraversion as defined by the Eysenck Personality Questionaire (EPQ). A total of 268 patients with anxiety disorder (AD), 541 with unipolar depression (MD), and 541 healthy controls were included. We observe associations for five tag‐SNPs with BI in the AD‐ and control samples as well as two additional case–control associations in the MD‐sample. The associated SNPs lie within a 16KB linkage disequilibrium‐block, including putative 5′ GAD2‐promoter‐elements as well as the 3′ end of the gene MYO3A. Using open access mRNA‐expression data, we could show that BI‐associated SNPs appear to be associated with differences in MYO3A‐ but not GAD2 lymphoblastoid‐mRNA expression levels. These results support earlier studies that suggest associations of polymorphisms within the GAD2 locus with anxiety and affective disorders. However, data from expression studies imply that these polymorphisms could tag functional effects on the neighboring gene MYO3A, which is also expressed in the brain, including the cingulate cortex and the amygdala. © 2009 Wiley‐Liss, Inc.</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1"><p>How to Cite this Article: Unschuld PG, Ising M, Specht M, Erhardt A, Ripke S, Heck A, Kloiber S, Straub V, Brueckl T, Müller‐Myhsok B, Holsboer F, Binder EB. 2009. Polymorphisms in the GAD2 Gene‐Region Are Associated With Susceptibility for Unipolar Depression and With a Risk Factor for Anxiety Disorders. Am J Med Genet Part B 150B:1100–1109.</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Polymorphisms in the GAD2 gene‐region are associated with susceptibility for unipolar depression and with a risk factor for anxiety disorders</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Polymorphisms in the GAD2 gene‐region are associated with susceptibility for unipolar depression and with a risk factor for anxiety disorders</title></titleInfo><name type="personal"><namePart type="given">Paul G.</namePart><namePart type="family">Unschuld</namePart><affiliation>Max Planck Institute of Psychiatry, München, Germany</affiliation><affiliation>Max Planck Institute of Psychiatry, Kraepelinstr. 2‐10, 80804 München, Germany.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Marcus</namePart><namePart type="family">Ising</namePart><affiliation>Max Planck Institute of Psychiatry, München, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Michael</namePart><namePart type="family">Specht</namePart><affiliation>Max Planck Institute of Psychiatry, München, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Angelika</namePart><namePart type="family">Erhardt</namePart><affiliation>Max Planck Institute of Psychiatry, München, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Stephan</namePart><namePart type="family">Ripke</namePart><affiliation>Max Planck Institute of Psychiatry, München, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Angela</namePart><namePart type="family">Heck</namePart><affiliation>Max Planck Institute of Psychiatry, München, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Stefan</namePart><namePart type="family">Kloiber</namePart><affiliation>Max Planck Institute of Psychiatry, München, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Verica</namePart><namePart type="family">Straub</namePart><affiliation>Max Planck Institute of Psychiatry, München, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Tanja</namePart><namePart type="family">Brueckl</namePart><affiliation>Max Planck Institute of Psychiatry, München, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Bertram</namePart><namePart type="family">Müller‐Myhsok</namePart><affiliation>Max Planck Institute of Psychiatry, München, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Florian</namePart><namePart type="family">Holsboer</namePart><affiliation>Max Planck Institute of Psychiatry, München, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Elisabeth B.</namePart><namePart type="family">Binder</namePart><affiliation>Max Planck Institute of Psychiatry, München, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2009-12-05</dateIssued><dateCaptured encoding="w3cdtf">2008-09-30</dateCaptured><dateValid encoding="w3cdtf">2009-01-14</dateValid><copyrightDate encoding="w3cdtf">2009</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">2</extent><extent unit="tables">3</extent><extent unit="references">67</extent><extent unit="words">7763</extent></physicalDescription><abstract lang="en">Glutamate decarboxylase (GAD) is the rate limiting enzyme for conversion of glutamic acid to gamma‐aminobutyric acid (GABA). The GAD 65 kDa isoform is encoded by the gene GAD2 and is mainly expressed in synaptic terminals. It serves as an apoenzyme, which shows enhanced availability in situations of stress, responding to short‐term demands for GABA. We analyzed 18 single nucleotide polymorphisms (SNPs) in the GAD2‐gene region for associations with psychiatric diagnosis and behavioral inhibition (BI) derived from the personality traits neuroticism and extraversion as defined by the Eysenck Personality Questionaire (EPQ). A total of 268 patients with anxiety disorder (AD), 541 with unipolar depression (MD), and 541 healthy controls were included. We observe associations for five tag‐SNPs with BI in the AD‐ and control samples as well as two additional case–control associations in the MD‐sample. The associated SNPs lie within a 16KB linkage disequilibrium‐block, including putative 5′ GAD2‐promoter‐elements as well as the 3′ end of the gene MYO3A. Using open access mRNA‐expression data, we could show that BI‐associated SNPs appear to be associated with differences in MYO3A‐ but not GAD2 lymphoblastoid‐mRNA expression levels. These results support earlier studies that suggest associations of polymorphisms within the GAD2 locus with anxiety and affective disorders. However, data from expression studies imply that these polymorphisms could tag functional effects on the neighboring gene MYO3A, which is also expressed in the brain, including the cingulate cortex and the amygdala. © 2009 Wiley‐Liss, Inc.</abstract><note type="content">*How to Cite this Article: Unschuld PG, Ising M, Specht M, Erhardt A, Ripke S, Heck A, Kloiber S, Straub V, Brueckl T, Müller‐Myhsok B, Holsboer F, Binder EB. 2009. Polymorphisms in the GAD2 Gene‐Region Are Associated With Susceptibility for Unipolar Depression and With a Risk Factor for Anxiety Disorders. Am J Med Genet Part B 150B:1100–1109.</note><note type="funding">Bavarian Ministry of Commerce</note><note type="funding">Federal Ministry of Education and Research (BMBF)</note><note type="funding">Förderkennzeichen - No. 01GS0481; </note><subject lang="en"><genre>keywords</genre><topic>genetics</topic><topic>association</topic><topic>SNP</topic><topic>MYO3A</topic><topic>behavioral inhibition</topic></subject><relatedItem type="host"><titleInfo><title>American Journal of Medical Genetics Part B: Neuropsychiatric Genetics</title></titleInfo><titleInfo type="abbreviated"><title>Am. J. Med. 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