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Preliminary evidence for a role of the adrenergic nervous system in generalized anxiety disorder

Identifieur interne : 000868 ( Pmc/Curation ); précédent : 000867; suivant : 000869

Preliminary evidence for a role of the adrenergic nervous system in generalized anxiety disorder

Auteurs : Xiaobin Zhang [France, République populaire de Chine] ; Joanna Norton [France] ; Isabelle Carrière [France] ; Karen Ritchie [France, Royaume-Uni] ; Isabelle Chaudieu [France] ; Joanne Ryan [France, Australie] ; Marie-Laure Ancelin [France]

Source :

RBID : PMC:5309880

Abstract

Generalized anxiety disorder (GAD) is a common chronic condition that is understudied compared to other psychiatric disorders. An altered adrenergic function has been reported in GAD, however direct evidence for genetic susceptibility is missing. This study evaluated the associations of gene variants in adrenergic receptors (ADRs) with GAD, with the involvement of stressful events. Data were obtained from 844 French community-dwelling elderly aged 65 or over. Anxiety disorders were assessed using the Mini-International Neuropsychiatry Interview, according to DSM-IV criteria. Eight single-nucleotide polymorphisms (SNPs) involved with adrenergic function were genotyped; adrenergic receptors alpha(1A) (ADRA1A), alpha(2A) (ADRA2A), and beta2 (ADRB2) and transcription factor TCF7L2. Questionnaires evaluated recent stressful life events as well as early environment during childhood and adolescence. Using multivariate logistic regression analyses four SNPs were significantly associated with GAD. A 4-fold modified risk was found with ADRA1A rs17426222 and rs573514, and ADRB2 rs1042713 which remained significant after Bonferroni correction. Certain variants may moderate the effect of adverse life events on the risk of GAD. Replication in larger samples is needed due to the small case number. This is the first study showing that ADR variants are susceptibility factors for GAD, further highlighting the critical role of the adrenergic nervous system in this disorder.


Url:
DOI: 10.1038/srep42676
PubMed: 28198454
PubMed Central: 5309880

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PMC:5309880

Le document en format XML

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<p>Generalized anxiety disorder (GAD) is a common chronic condition that is understudied compared to other psychiatric disorders. An altered adrenergic function has been reported in GAD, however direct evidence for genetic susceptibility is missing. This study evaluated the associations of gene variants in adrenergic receptors (
<italic>ADRs</italic>
) with GAD, with the involvement of stressful events. Data were obtained from 844 French community-dwelling elderly aged 65 or over. Anxiety disorders were assessed using the Mini-International Neuropsychiatry Interview, according to DSM-IV criteria. Eight single-nucleotide polymorphisms (SNPs) involved with adrenergic function were genotyped; adrenergic receptors alpha(1A) (
<italic>ADRA1A</italic>
), alpha(2A) (
<italic>ADRA2A</italic>
), and beta2 (
<italic>ADRB2</italic>
) and transcription factor
<italic>TCF7L2</italic>
. Questionnaires evaluated recent stressful life events as well as early environment during childhood and adolescence. Using multivariate logistic regression analyses four SNPs were significantly associated with GAD. A 4-fold modified risk was found with
<italic>ADRA1A rs17426222</italic>
and
<italic>rs573514,</italic>
and
<italic>ADRB2 rs1042713</italic>
which remained significant after Bonferroni correction. Certain variants may moderate the effect of adverse life events on the risk of GAD. Replication in larger samples is needed due to the small case number. This is the first study showing that
<italic>ADR</italic>
variants are susceptibility factors for GAD, further highlighting the critical role of the adrenergic nervous system in this disorder.</p>
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</TEI>
<pmc article-type="research-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Sci Rep</journal-id>
<journal-id journal-id-type="iso-abbrev">Sci Rep</journal-id>
<journal-title-group>
<journal-title>Scientific Reports</journal-title>
</journal-title-group>
<issn pub-type="epub">2045-2322</issn>
<publisher>
<publisher-name>Nature Publishing Group</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">28198454</article-id>
<article-id pub-id-type="pmc">5309880</article-id>
<article-id pub-id-type="pii">srep42676</article-id>
<article-id pub-id-type="doi">10.1038/srep42676</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Preliminary evidence for a role of the adrenergic nervous system in generalized anxiety disorder</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Zhang</surname>
<given-names>Xiaobin</given-names>
</name>
<xref ref-type="aff" rid="a1">1</xref>
<xref ref-type="aff" rid="a2">2</xref>
<xref ref-type="aff" rid="a3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Norton</surname>
<given-names>Joanna</given-names>
</name>
<xref ref-type="aff" rid="a1">1</xref>
<xref ref-type="aff" rid="a2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Carrière</surname>
<given-names>Isabelle</given-names>
</name>
<xref ref-type="aff" rid="a1">1</xref>
<xref ref-type="aff" rid="a2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ritchie</surname>
<given-names>Karen</given-names>
</name>
<xref ref-type="aff" rid="a1">1</xref>
<xref ref-type="aff" rid="a2">2</xref>
<xref ref-type="aff" rid="a4">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Chaudieu</surname>
<given-names>Isabelle</given-names>
</name>
<xref ref-type="aff" rid="a1">1</xref>
<xref ref-type="aff" rid="a2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ryan</surname>
<given-names>Joanne</given-names>
</name>
<xref ref-type="aff" rid="a1">1</xref>
<xref ref-type="aff" rid="a2">2</xref>
<xref ref-type="aff" rid="a5">5</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ancelin</surname>
<given-names>Marie-Laure</given-names>
</name>
<xref ref-type="corresp" rid="c1">a</xref>
<xref ref-type="aff" rid="a1">1</xref>
<xref ref-type="aff" rid="a2">2</xref>
</contrib>
<aff id="a1">
<label>1</label>
<institution>Inserm</institution>
, U1061, Montpellier,
<country>France</country>
</aff>
<aff id="a2">
<label>2</label>
<institution>Univ Montpellier</institution>
, Montpellier,
<country>France</country>
</aff>
<aff id="a3">
<label>3</label>
<institution>Tianjin Mental Health Center</institution>
, Tianjin,
<country>China</country>
</aff>
<aff id="a4">
<label>4</label>
<institution>Faculty of Medicine, Imperial College</institution>
, London,
<country>UK</country>
</aff>
<aff id="a5">
<label>5</label>
<institution>Disease Epigenetics Group, Murdoch Children’s Research Institute, and Department of Paediatrics, The University of Melbourne</institution>
, Parkville,
<country>Australia</country>
</aff>
</contrib-group>
<author-notes>
<corresp id="c1">
<label>a</label>
<email>marie-laure.ancelin@inserm.fr</email>
</corresp>
</author-notes>
<pub-date pub-type="epub">
<day>15</day>
<month>02</month>
<year>2017</year>
</pub-date>
<pub-date pub-type="collection">
<year>2017</year>
</pub-date>
<volume>7</volume>
<elocation-id>42676</elocation-id>
<history>
<date date-type="received">
<day>02</day>
<month>10</month>
<year>2015</year>
</date>
<date date-type="accepted">
<day>13</day>
<month>01</month>
<year>2017</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright © 2017, The Author(s)</copyright-statement>
<copyright-year>2017</copyright-year>
<copyright-holder>The Author(s)</copyright-holder>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/">
<pmc-comment>author-paid</pmc-comment>
<license-p>This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
</license-p>
</license>
</permissions>
<abstract>
<p>Generalized anxiety disorder (GAD) is a common chronic condition that is understudied compared to other psychiatric disorders. An altered adrenergic function has been reported in GAD, however direct evidence for genetic susceptibility is missing. This study evaluated the associations of gene variants in adrenergic receptors (
<italic>ADRs</italic>
) with GAD, with the involvement of stressful events. Data were obtained from 844 French community-dwelling elderly aged 65 or over. Anxiety disorders were assessed using the Mini-International Neuropsychiatry Interview, according to DSM-IV criteria. Eight single-nucleotide polymorphisms (SNPs) involved with adrenergic function were genotyped; adrenergic receptors alpha(1A) (
<italic>ADRA1A</italic>
), alpha(2A) (
<italic>ADRA2A</italic>
), and beta2 (
<italic>ADRB2</italic>
) and transcription factor
<italic>TCF7L2</italic>
. Questionnaires evaluated recent stressful life events as well as early environment during childhood and adolescence. Using multivariate logistic regression analyses four SNPs were significantly associated with GAD. A 4-fold modified risk was found with
<italic>ADRA1A rs17426222</italic>
and
<italic>rs573514,</italic>
and
<italic>ADRB2 rs1042713</italic>
which remained significant after Bonferroni correction. Certain variants may moderate the effect of adverse life events on the risk of GAD. Replication in larger samples is needed due to the small case number. This is the first study showing that
<italic>ADR</italic>
variants are susceptibility factors for GAD, further highlighting the critical role of the adrenergic nervous system in this disorder.</p>
</abstract>
</article-meta>
</front>
<floats-group>
<table-wrap position="float" id="t1">
<label>Table 1</label>
<caption>
<title>Characteristics of participants according to current GAD
<xref ref-type="fn" rid="t1-fn1">a</xref>
in an elderly cohort (n = 844
<xref ref-type="fn" rid="t1-fn2">b</xref>
).</title>
</caption>
<table frame="hsides" rules="groups" border="1">
<colgroup>
<col align="left"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
</colgroup>
<thead valign="bottom">
<tr>
<th align="left" valign="top" charoff="50">Characteristic</th>
<th colspan="2" align="center" valign="top" charoff="50">No GAD
<hr></hr>
</th>
<th colspan="2" align="center" valign="top" charoff="50">GAD (n = 37)
<hr></hr>
</th>
<th colspan="3" align="center" valign="top" charoff="50">GAD
<italic>versus</italic>
no GAD
<hr></hr>
</th>
</tr>
<tr>
<th align="left" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50">Mean</th>
<th align="center" valign="top" charoff="50">SD</th>
<th align="center" valign="top" charoff="50">Mean</th>
<th align="center" valign="top" charoff="50">SD</th>
<th align="center" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50">P</th>
</tr>
<tr>
<th align="left" valign="top" charoff="50">Age</th>
<th align="center" valign="top" charoff="50">71.55</th>
<th align="center" valign="top" charoff="50">4.47</th>
<th align="center" valign="top" charoff="50">70.97</th>
<th align="center" valign="top" charoff="50">4.10</th>
<th align="center" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50">0.44</th>
</tr>
<tr>
<th align="left" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50">N</th>
<th align="center" valign="top" charoff="50">%</th>
<th align="center" valign="top" charoff="50">N</th>
<th align="center" valign="top" charoff="50">%</th>
<th align="center" valign="top" charoff="50">OR
<xref ref-type="fn" rid="t1-fn3">c</xref>
</th>
<th align="center" valign="top" charoff="50">95% CI</th>
<th align="center" valign="top" charoff="50">p</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td align="left" valign="top" charoff="50">Sex (female)</td>
<td align="center" valign="top" charoff="50">461</td>
<td align="center" valign="top" charoff="50">57.13</td>
<td align="center" valign="top" charoff="50">28</td>
<td align="center" valign="top" charoff="50">75.68</td>
<td align="center" valign="top" charoff="50">2.35</td>
<td align="center" valign="top" charoff="50">1.10–5.05</td>
<td align="center" valign="top" charoff="50">0.03</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Education level (
<underline>></underline>
5 years)</td>
<td align="center" valign="top" charoff="50">442</td>
<td align="center" valign="top" charoff="50">54.77</td>
<td align="center" valign="top" charoff="50">15</td>
<td align="center" valign="top" charoff="50">40.54</td>
<td align="center" valign="top" charoff="50">0.63</td>
<td align="center" valign="top" charoff="50">0.32–1.24</td>
<td align="center" valign="top" charoff="50">0.18</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">BMI (≥25 kg/m
<sup>2</sup>
)</td>
<td align="center" valign="top" charoff="50">346</td>
<td align="center" valign="top" charoff="50">42.87</td>
<td align="center" valign="top" charoff="50">8</td>
<td align="center" valign="top" charoff="50">21.62</td>
<td align="center" valign="top" charoff="50">0.42</td>
<td align="center" valign="top" charoff="50">0.19–0.93</td>
<td align="center" valign="top" charoff="50">0.03</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">At least one recent adverse events during the past year</td>
<td align="center" valign="top" charoff="50">463</td>
<td align="center" valign="top" charoff="50">57.37</td>
<td align="center" valign="top" charoff="50">29</td>
<td align="center" valign="top" charoff="50">78.38</td>
<td align="center" valign="top" charoff="50">2.68</td>
<td align="center" valign="top" charoff="50">1.21–5.96</td>
<td align="center" valign="top" charoff="50">0.02</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Low affective support</td>
<td align="center" valign="top" charoff="50">111</td>
<td align="center" valign="top" charoff="50">13.75</td>
<td align="center" valign="top" charoff="50">13</td>
<td align="center" valign="top" charoff="50">35.14</td>
<td align="center" valign="top" charoff="50">3.28</td>
<td align="center" valign="top" charoff="50">1.62–6.67</td>
<td align="center" valign="top" charoff="50">0.001</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Hypercholesterolemia (cholesterol ≥6.2 mmol/L or treated)</td>
<td align="center" valign="top" charoff="50">451</td>
<td align="center" valign="top" charoff="50">56.09</td>
<td align="center" valign="top" charoff="50">21</td>
<td align="center" valign="top" charoff="50">56.76</td>
<td align="center" valign="top" charoff="50">0.87</td>
<td align="center" valign="top" charoff="50">0.44–1.71</td>
<td align="center" valign="top" charoff="50">0.68</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Hypertension (resting blood pressure ≥160/95 mm Hg or treated)</td>
<td align="center" valign="top" charoff="50">321</td>
<td align="center" valign="top" charoff="50">39.78</td>
<td align="center" valign="top" charoff="50">14</td>
<td align="center" valign="top" charoff="50">37.84</td>
<td align="center" valign="top" charoff="50">1.03</td>
<td align="center" valign="top" charoff="50">0.52–2.05</td>
<td align="center" valign="top" charoff="50">0.93</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Ischemic pathologies
<xref ref-type="fn" rid="t1-fn4">d</xref>
</td>
<td align="center" valign="top" charoff="50">82</td>
<td align="center" valign="top" charoff="50">10.16</td>
<td align="center" valign="top" charoff="50">4</td>
<td align="center" valign="top" charoff="50">10.81</td>
<td align="center" valign="top" charoff="50">1.35</td>
<td align="center" valign="top" charoff="50">0.46–3.99</td>
<td align="center" valign="top" charoff="50">0.59</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Arrhythmia and heart failure</td>
<td align="center" valign="top" charoff="50">97</td>
<td align="center" valign="top" charoff="50">12.03</td>
<td align="center" valign="top" charoff="50">6</td>
<td align="center" valign="top" charoff="50">16.22</td>
<td align="center" valign="top" charoff="50">1.52</td>
<td align="center" valign="top" charoff="50">0.61–3.77</td>
<td align="center" valign="top" charoff="50">0.37</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">At least one chronic disorder
<xref ref-type="fn" rid="t1-fn5">e</xref>
</td>
<td align="center" valign="top" charoff="50">469</td>
<td align="center" valign="top" charoff="50">58.12</td>
<td align="center" valign="top" charoff="50">20</td>
<td align="center" valign="top" charoff="50">54.05</td>
<td align="center" valign="top" charoff="50">0.91</td>
<td align="center" valign="top" charoff="50">0.47–1.77</td>
<td align="center" valign="top" charoff="50">0.78</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">MMSE (<26)</td>
<td align="center" valign="top" charoff="50">76</td>
<td align="center" valign="top" charoff="50">9.43</td>
<td align="center" valign="top" charoff="50">5</td>
<td align="center" valign="top" charoff="50">13.51</td>
<td align="center" valign="top" charoff="50">1.38</td>
<td align="center" valign="top" charoff="50">0.52–3.67</td>
<td align="center" valign="top" charoff="50">0.52</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Use of psychotropic medication</td>
<td align="center" valign="top" charoff="50">80</td>
<td align="center" valign="top" charoff="50">9.91</td>
<td align="center" valign="top" charoff="50">10</td>
<td align="center" valign="top" charoff="50">27.03</td>
<td align="center" valign="top" charoff="50">3.02</td>
<td align="center" valign="top" charoff="50">1.38–6.62</td>
<td align="center" valign="top" charoff="50">0.006</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Major depression</td>
<td align="center" valign="top" charoff="50">11</td>
<td align="center" valign="top" charoff="50">1.38</td>
<td align="center" valign="top" charoff="50">5</td>
<td align="center" valign="top" charoff="50">13.51</td>
<td align="center" valign="top" charoff="50">10.04</td>
<td align="center" valign="top" charoff="50">3.24–31.1</td>
<td align="center" valign="top" charoff="50"><0.0001</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Anxiety disorder (without GAD)</td>
<td align="center" valign="top" charoff="50">69</td>
<td align="center" valign="top" charoff="50">8.55</td>
<td align="center" valign="top" charoff="50">12</td>
<td align="center" valign="top" charoff="50">32.43</td>
<td align="center" valign="top" charoff="50">4.40</td>
<td align="center" valign="top" charoff="50">2.11–9.37</td>
<td align="center" valign="top" charoff="50"><0.0001</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Phobia</td>
<td align="center" valign="top" charoff="50">64</td>
<td align="center" valign="top" charoff="50">7.93</td>
<td align="center" valign="top" charoff="50">12</td>
<td align="center" valign="top" charoff="50">32.43</td>
<td align="center" valign="top" charoff="50">4.81</td>
<td align="center" valign="top" charoff="50">2.27–10.2</td>
<td align="center" valign="top" charoff="50"><0.0001</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Post-traumatic stress disorder</td>
<td align="center" valign="top" charoff="50">1</td>
<td align="center" valign="top" charoff="50">0.12</td>
<td align="center" valign="top" charoff="50">1</td>
<td align="center" valign="top" charoff="50">2.70</td>
<td align="center" valign="top" charoff="50">n.a</td>
<td align="center" valign="top" charoff="50">n.a</td>
<td align="center" valign="top" charoff="50">n.a</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Panic disorder</td>
<td align="center" valign="top" charoff="50">1</td>
<td align="center" valign="top" charoff="50">0.12</td>
<td align="center" valign="top" charoff="50">0</td>
<td align="center" valign="top" charoff="50">0.00</td>
<td align="center" valign="top" charoff="50">n.a</td>
<td align="center" valign="top" charoff="50">n.a</td>
<td align="center" valign="top" charoff="50">n.a</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Obsessive compulsive disorder</td>
<td align="center" valign="top" charoff="50">4</td>
<td align="center" valign="top" charoff="50">0.50</td>
<td align="center" valign="top" charoff="50">1</td>
<td align="center" valign="top" charoff="50">2.70</td>
<td align="center" valign="top" charoff="50">n.a</td>
<td align="center" valign="top" charoff="50">n.a</td>
<td align="center" valign="top" charoff="50">n.a</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="t1-fn1">
<p>
<sup>a</sup>
The diagnosis of GAD and other psychiatric disorders was performed using the MINI and according to DSM-IV criteria (see Methods).</p>
</fn>
<fn id="t1-fn2">
<p>
<sup>b</sup>
Except for hypercholesterolemia (n = 841); arrhythmia and heart failure and MMSE (n = 843); major depression (n = 837).</p>
</fn>
<fn id="t1-fn3">
<p>
<sup>c</sup>
Adjusted for age (continuous) and sex.</p>
</fn>
<fn id="t1-fn4">
<p>
<sup>d</sup>
Ischemic pathologies correspond to angina pectoris, myocardial infarction, stroke, cardiovascular surgery, and arteritis.</p>
</fn>
<fn id="t1-fn5">
<p>
<sup>e</sup>
Chronic disorders correspond to hypercholesterolemia, hypertension, diabetes, asthma, osteoporosis, thyroid disorder, and recent cancer.</p>
</fn>
<fn id="t1-fn6">
<p>n.a.: not applicable due to the low number of participants.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap position="float" id="t2">
<label>Table 2</label>
<caption>
<title>Logistic regression analysis for the association between
<italic>ADR</italic>
polymorphisms and current GAD in an elderly cohort
<xref ref-type="fn" rid="t2-fn1">a</xref>
.</title>
</caption>
<table frame="hsides" rules="groups" border="1">
<colgroup>
<col align="left"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
</colgroup>
<thead valign="bottom">
<tr>
<th rowspan="2" align="left" valign="top" charoff="50">
<italic>Gene</italic>
</th>
<th colspan="2" align="center" valign="top" charoff="50">
<italic>SNPs and genotype</italic>
</th>
<th colspan="2" align="center" valign="top" charoff="50">No GAD
<hr></hr>
</th>
<th colspan="2" align="center" valign="top" charoff="50">GAD
<hr></hr>
</th>
<th colspan="3" align="center" valign="top" charoff="50">Odds of pure phobia
<italic>versus</italic>
no GAD
<hr></hr>
</th>
</tr>
<tr>
<th colspan="2" align="center" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50">N</th>
<th align="center" valign="top" charoff="50">%</th>
<th align="center" valign="top" charoff="50">N</th>
<th align="center" valign="top" charoff="50">%</th>
<th align="center" valign="top" charoff="50">OR
<xref ref-type="fn" rid="t2-fn1">a</xref>
</th>
<th align="center" valign="top" charoff="50">95% CI</th>
<th align="center" valign="top" charoff="50">p</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td rowspan="11" align="left" valign="middle" charoff="50">
<italic>
<bold>ADRA1A</bold>
</italic>
</td>
<td rowspan="3" align="center" valign="middle" charoff="50">
<italic>rs4732682</italic>
</td>
<td align="center" valign="top" charoff="50">CC</td>
<td align="center" valign="top" charoff="50">225</td>
<td align="center" valign="top" charoff="50">29.7</td>
<td align="center" valign="top" charoff="50">17</td>
<td align="center" valign="top" charoff="50">47.2</td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">CT</td>
<td align="center" valign="top" charoff="50">386</td>
<td align="center" valign="top" charoff="50">51.0</td>
<td align="center" valign="top" charoff="50">15</td>
<td align="center" valign="top" charoff="50">41.7</td>
<td align="center" valign="top" charoff="50">0.51</td>
<td align="center" valign="top" charoff="50">0.25–1.04</td>
<td align="center" valign="top" charoff="50">0.06</td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">TT</td>
<td align="center" valign="top" charoff="50">146</td>
<td align="center" valign="top" charoff="50">19.3</td>
<td align="center" valign="top" charoff="50">4</td>
<td align="center" valign="top" charoff="50">11.1</td>
<td align="center" valign="top" charoff="50">0.36</td>
<td align="center" valign="top" charoff="50">0.12–1.09</td>
<td align="center" valign="top" charoff="50">0.07</td>
</tr>
<tr>
<td rowspan="3" align="center" valign="middle" charoff="50">
<italic>rs17426222</italic>
</td>
<td align="center" valign="top" charoff="50">CC</td>
<td align="center" valign="top" charoff="50">433</td>
<td align="center" valign="top" charoff="50">54.0</td>
<td align="center" valign="top" charoff="50">13</td>
<td align="center" valign="top" charoff="50">35.1</td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">CT</td>
<td align="center" valign="top" charoff="50">315</td>
<td align="center" valign="top" charoff="50">39.3</td>
<td align="center" valign="top" charoff="50">17</td>
<td align="center" valign="top" charoff="50">46.0</td>
<td align="center" valign="top" charoff="50">1.81</td>
<td align="center" valign="top" charoff="50">0.86–3.79</td>
<td align="center" valign="top" charoff="50">0.12</td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">TT</td>
<td align="center" valign="top" charoff="50">54</td>
<td align="center" valign="top" charoff="50">6.7</td>
<td align="center" valign="top" charoff="50">7</td>
<td align="center" valign="top" charoff="50">18.9</td>
<td align="center" valign="top" charoff="50">4.34</td>
<td align="center" valign="top" charoff="50">1.65–11.4</td>
<td align="center" valign="top" charoff="50">0.003</td>
</tr>
<tr>
<td rowspan="2" align="center" valign="middle" charoff="50">
<italic>rs3808585</italic>
</td>
<td align="center" valign="top" charoff="50">CC</td>
<td align="center" valign="top" charoff="50">418</td>
<td align="center" valign="top" charoff="50">52.6</td>
<td align="center" valign="top" charoff="50">21</td>
<td align="center" valign="top" charoff="50">56.8</td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">CT/TT</td>
<td align="center" valign="top" charoff="50">376</td>
<td align="center" valign="top" charoff="50">47.4</td>
<td align="center" valign="top" charoff="50">16</td>
<td align="center" valign="top" charoff="50">43.2</td>
<td align="center" valign="top" charoff="50">0.84</td>
<td align="center" valign="top" charoff="50">0.43–1.64</td>
<td align="center" valign="top" charoff="50">0.61</td>
</tr>
<tr>
<td rowspan="3" align="center" valign="middle" charoff="50">
<italic>rs573514</italic>
</td>
<td align="center" valign="top" charoff="50">TT</td>
<td align="center" valign="top" charoff="50">224</td>
<td align="center" valign="top" charoff="50">28.6</td>
<td align="center" valign="top" charoff="50">5</td>
<td align="center" valign="top" charoff="50">14.3</td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">CT</td>
<td align="center" valign="top" charoff="50">414</td>
<td align="center" valign="top" charoff="50">52.9</td>
<td align="center" valign="top" charoff="50">15</td>
<td align="center" valign="top" charoff="50">42.9</td>
<td align="center" valign="top" charoff="50">1.58</td>
<td align="center" valign="top" charoff="50">0.56–4.41</td>
<td align="center" valign="top" charoff="50">0.39</td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">CC</td>
<td align="center" valign="top" charoff="50">145</td>
<td align="center" valign="top" charoff="50">18.5</td>
<td align="center" valign="top" charoff="50">15</td>
<td align="center" valign="top" charoff="50">42.9</td>
<td align="center" valign="top" charoff="50">4.48</td>
<td align="center" valign="top" charoff="50">1.59–12.7</td>
<td align="center" valign="top" charoff="50">0.005</td>
</tr>
<tr>
<td rowspan="4" align="left" valign="middle" charoff="50">
<italic>
<bold>ADRA2A</bold>
</italic>
</td>
<td rowspan="2" align="center" valign="middle" charoff="50">
<italic>rs1800544</italic>
</td>
<td align="center" valign="top" charoff="50">CC</td>
<td align="center" valign="top" charoff="50">422</td>
<td align="center" valign="top" charoff="50">54.4</td>
<td align="center" valign="top" charoff="50">20</td>
<td align="center" valign="top" charoff="50">54.1</td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">CT/TT</td>
<td align="center" valign="top" charoff="50">353</td>
<td align="center" valign="top" charoff="50">45.6</td>
<td align="center" valign="top" charoff="50">17</td>
<td align="center" valign="top" charoff="50">45.9</td>
<td align="center" valign="top" charoff="50">0.97</td>
<td align="center" valign="top" charoff="50">0.50–1.89</td>
<td align="center" valign="top" charoff="50">0.94</td>
</tr>
<tr>
<td rowspan="2" align="center" valign="middle" charoff="50">
<italic>rs11195419</italic>
</td>
<td align="center" valign="top" charoff="50">CC</td>
<td align="center" valign="top" charoff="50">650</td>
<td align="center" valign="top" charoff="50">82.7</td>
<td align="center" valign="top" charoff="50">29</td>
<td align="center" valign="top" charoff="50">78.4</td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">AA/AC</td>
<td align="center" valign="top" charoff="50">136</td>
<td align="center" valign="top" charoff="50">17.3</td>
<td align="center" valign="top" charoff="50">8</td>
<td align="center" valign="top" charoff="50">21.6</td>
<td align="center" valign="top" charoff="50">1.34</td>
<td align="center" valign="top" charoff="50">0.60–3.01</td>
<td align="center" valign="top" charoff="50">0.47</td>
</tr>
<tr>
<td rowspan="3" align="left" valign="middle" charoff="50">
<italic>
<bold>TCF7L2</bold>
</italic>
</td>
<td rowspan="3" align="center" valign="middle" charoff="50">
<italic>rs7903146</italic>
</td>
<td align="center" valign="top" charoff="50">CC</td>
<td align="center" valign="top" charoff="50">340</td>
<td align="center" valign="top" charoff="50">43.5</td>
<td align="center" valign="top" charoff="50">10</td>
<td align="center" valign="top" charoff="50">27.8</td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">CT</td>
<td align="center" valign="top" charoff="50">358</td>
<td align="center" valign="top" charoff="50">45.8</td>
<td align="center" valign="top" charoff="50">18</td>
<td align="center" valign="top" charoff="50">50.0</td>
<td align="center" valign="top" charoff="50">1.68</td>
<td align="center" valign="top" charoff="50">0.76–3.70</td>
<td align="center" valign="top" charoff="50">0.20</td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">TT</td>
<td align="center" valign="top" charoff="50">84</td>
<td align="center" valign="top" charoff="50">10.7</td>
<td align="center" valign="top" charoff="50">8</td>
<td align="center" valign="top" charoff="50">22.2</td>
<td align="center" valign="top" charoff="50">3.23</td>
<td align="center" valign="top" charoff="50">1.23–8.52</td>
<td align="center" valign="top" charoff="50">0.018</td>
</tr>
<tr>
<td rowspan="3" align="left" valign="middle" charoff="50">
<italic>
<bold>ADRB2</bold>
</italic>
</td>
<td rowspan="3" align="center" valign="middle" charoff="50">
<italic>rs1042713</italic>
</td>
<td align="center" valign="top" charoff="50">AA</td>
<td align="center" valign="top" charoff="50">110</td>
<td align="center" valign="top" charoff="50">13.8</td>
<td align="center" valign="top" charoff="50">9</td>
<td align="center" valign="top" charoff="50">24.3</td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">AG</td>
<td align="center" valign="top" charoff="50">372</td>
<td align="center" valign="top" charoff="50">46.7</td>
<td align="center" valign="top" charoff="50">9</td>
<td align="center" valign="top" charoff="50">24.3</td>
<td align="center" valign="top" charoff="50">0.28</td>
<td align="center" valign="top" charoff="50">0.11–0.73</td>
<td align="center" valign="top" charoff="50">0.009</td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">GG</td>
<td align="center" valign="top" charoff="50">314</td>
<td align="center" valign="top" charoff="50">39.5</td>
<td align="center" valign="top" charoff="50">19</td>
<td align="center" valign="top" charoff="50">51.4</td>
<td align="center" valign="top" charoff="50">0.73</td>
<td align="center" valign="top" charoff="50">0.32–1.67</td>
<td align="center" valign="top" charoff="50">0.45</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="t2-fn1">
<p>
<sup>a</sup>
Adjusted for age and sex.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap position="float" id="t3">
<label>Table 3</label>
<caption>
<title>Logistic regression analysis for the association between
<italic>ADR</italic>
polymorphisms and current phobia
<sup>a</sup>
.</title>
</caption>
<table frame="hsides" rules="groups" border="1">
<colgroup>
<col align="left"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
</colgroup>
<thead valign="bottom">
<tr>
<th rowspan="2" align="left" valign="middle" charoff="50">
<italic>Gene</italic>
</th>
<th colspan="2" align="center" valign="top" charoff="50">
<italic>SNPs and genotype</italic>
</th>
<th colspan="2" align="center" valign="top" charoff="50">No phobia
<hr></hr>
</th>
<th colspan="2" align="center" valign="top" charoff="50">Pure phobia
<hr></hr>
</th>
<th colspan="3" align="center" valign="top" charoff="50">Odds of pure phobia
<italic>versus</italic>
no phobia
<hr></hr>
</th>
</tr>
<tr>
<th align="center" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50">N</th>
<th align="center" valign="top" charoff="50">%</th>
<th align="center" valign="top" charoff="50">N</th>
<th align="center" valign="top" charoff="50">%</th>
<th align="center" valign="top" charoff="50">OR</th>
<th align="center" valign="top" charoff="50">95% CI</th>
<th align="center" valign="top" charoff="50">p</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td rowspan="11" align="left" valign="middle" charoff="50">
<italic>
<bold>ADRA1A</bold>
</italic>
</td>
<td rowspan="3" align="center" valign="middle" charoff="50">
<italic>rs4732682</italic>
</td>
<td align="center" valign="top" charoff="50">CC</td>
<td align="center" valign="top" charoff="50">214</td>
<td align="center" valign="top" charoff="50">30.75</td>
<td align="center" valign="top" charoff="50">11</td>
<td align="center" valign="top" charoff="50">18.03</td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">CT</td>
<td align="center" valign="top" charoff="50">350</td>
<td align="center" valign="top" charoff="50">50.29</td>
<td align="center" valign="top" charoff="50">36</td>
<td align="center" valign="top" charoff="50">59.02</td>
<td align="center" valign="top" charoff="50">1.95</td>
<td align="center" valign="top" charoff="50">0.97–3.94</td>
<td align="center" valign="top" charoff="50">0.06</td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">TT</td>
<td align="center" valign="top" charoff="50">132</td>
<td align="center" valign="top" charoff="50">18.97</td>
<td align="center" valign="top" charoff="50">14</td>
<td align="center" valign="top" charoff="50">22.95</td>
<td align="center" valign="top" charoff="50">2.04</td>
<td align="center" valign="top" charoff="50">0.89–4.68</td>
<td align="center" valign="top" charoff="50">0.09</td>
</tr>
<tr>
<td rowspan="3" align="center" valign="middle" charoff="50">
<italic>rs17426222</italic>
</td>
<td align="center" valign="top" charoff="50">CC</td>
<td align="center" valign="top" charoff="50">399</td>
<td align="center" valign="top" charoff="50">54.21</td>
<td align="center" valign="top" charoff="50">34</td>
<td align="center" valign="top" charoff="50">51.52</td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">CT</td>
<td align="center" valign="top" charoff="50">290</td>
<td align="center" valign="top" charoff="50">39.40</td>
<td align="center" valign="top" charoff="50">25</td>
<td align="center" valign="top" charoff="50">37.88</td>
<td align="center" valign="top" charoff="50">1.03</td>
<td align="center" valign="top" charoff="50">0.59–1.77</td>
<td align="center" valign="top" charoff="50">0.93</td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">TT</td>
<td align="center" valign="top" charoff="50">47</td>
<td align="center" valign="top" charoff="50">6.39</td>
<td align="center" valign="top" charoff="50">7</td>
<td align="center" valign="top" charoff="50">10.61</td>
<td align="center" valign="top" charoff="50">1.81</td>
<td align="center" valign="top" charoff="50">0.75–4.37</td>
<td align="center" valign="top" charoff="50">0.19</td>
</tr>
<tr>
<td rowspan="2" align="center" valign="middle" charoff="50">
<italic>rs3808585</italic>
</td>
<td align="center" valign="top" charoff="50">CC</td>
<td align="center" valign="top" charoff="50">388</td>
<td align="center" valign="top" charoff="50">53.22</td>
<td align="center" valign="top" charoff="50">30</td>
<td align="center" valign="top" charoff="50">46.15</td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">CT/TT</td>
<td align="center" valign="top" charoff="50">341</td>
<td align="center" valign="top" charoff="50">46.78</td>
<td align="center" valign="top" charoff="50">35</td>
<td align="center" valign="top" charoff="50">53.85</td>
<td align="center" valign="top" charoff="50">1.30</td>
<td align="center" valign="top" charoff="50">0.77–2.18</td>
<td align="center" valign="top" charoff="50">0.32</td>
</tr>
<tr>
<td rowspan="3" align="center" valign="middle" charoff="50">
<italic>rs573514</italic>
</td>
<td align="center" valign="top" charoff="50">TT</td>
<td align="center" valign="top" charoff="50">206</td>
<td align="center" valign="top" charoff="50">28.57</td>
<td align="center" valign="top" charoff="50">18</td>
<td align="center" valign="top" charoff="50">29.03</td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">CT</td>
<td align="center" valign="top" charoff="50">381</td>
<td align="center" valign="top" charoff="50">52.84</td>
<td align="center" valign="top" charoff="50">33</td>
<td align="center" valign="top" charoff="50">53.23</td>
<td align="center" valign="top" charoff="50">0.96</td>
<td align="center" valign="top" charoff="50">0.52–1.77</td>
<td align="center" valign="top" charoff="50">0.90</td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">CC</td>
<td align="center" valign="top" charoff="50">134</td>
<td align="center" valign="top" charoff="50">18.59</td>
<td align="center" valign="top" charoff="50">11</td>
<td align="center" valign="top" charoff="50">17.74</td>
<td align="center" valign="top" charoff="50">0.92</td>
<td align="center" valign="top" charoff="50">0.42–2.03</td>
<td align="center" valign="top" charoff="50">0.83</td>
</tr>
<tr>
<td rowspan="4" align="left" valign="middle" charoff="50">
<italic>
<bold>ADRA2A</bold>
</italic>
</td>
<td rowspan="2" align="center" valign="middle" charoff="50">
<italic>rs1800544</italic>
</td>
<td align="center" valign="top" charoff="50">CC</td>
<td align="center" valign="top" charoff="50">389</td>
<td align="center" valign="top" charoff="50">54.33</td>
<td align="center" valign="top" charoff="50">33</td>
<td align="center" valign="top" charoff="50">55.00</td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">CT/TT</td>
<td align="center" valign="top" charoff="50">327</td>
<td align="center" valign="top" charoff="50">45.67</td>
<td align="center" valign="top" charoff="50">27</td>
<td align="center" valign="top" charoff="50">45.00</td>
<td align="center" valign="top" charoff="50">0.92</td>
<td align="center" valign="top" charoff="50">0.54–1.57</td>
<td align="center" valign="top" charoff="50">0.76</td>
</tr>
<tr>
<td rowspan="2" align="center" valign="middle" charoff="50">
<italic>rs11195419</italic>
</td>
<td align="center" valign="top" charoff="50">CC</td>
<td align="center" valign="top" charoff="50">597</td>
<td align="center" valign="top" charoff="50">82.46</td>
<td align="center" valign="top" charoff="50">53</td>
<td align="center" valign="top" charoff="50">85.48</td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">AA/AC</td>
<td align="center" valign="top" charoff="50">127</td>
<td align="center" valign="top" charoff="50">17.54</td>
<td align="center" valign="top" charoff="50">9</td>
<td align="center" valign="top" charoff="50">14.52</td>
<td align="center" valign="top" charoff="50">0.82</td>
<td align="center" valign="top" charoff="50">0.39–1.71</td>
<td align="center" valign="top" charoff="50">0.59</td>
</tr>
<tr>
<td rowspan="3" align="left" valign="middle" charoff="50">
<italic>
<bold>TCF7L2</bold>
</italic>
</td>
<td rowspan="3" align="center" valign="middle" charoff="50">
<italic>rs7903146</italic>
</td>
<td align="center" valign="top" charoff="50">CC</td>
<td align="center" valign="top" charoff="50">310</td>
<td align="center" valign="top" charoff="50">43.00</td>
<td align="center" valign="top" charoff="50">30</td>
<td align="center" valign="top" charoff="50">49.18</td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">CT</td>
<td align="center" valign="top" charoff="50">333</td>
<td align="center" valign="top" charoff="50">46.19</td>
<td align="center" valign="top" charoff="50">25</td>
<td align="center" valign="top" charoff="50">40.98</td>
<td align="center" valign="top" charoff="50">0.77</td>
<td align="center" valign="top" charoff="50">0.44–1.36</td>
<td align="center" valign="top" charoff="50">0.37</td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">TT</td>
<td align="center" valign="top" charoff="50">78</td>
<td align="center" valign="top" charoff="50">10.82</td>
<td align="center" valign="top" charoff="50">6</td>
<td align="center" valign="top" charoff="50">9.84</td>
<td align="center" valign="top" charoff="50">0.81</td>
<td align="center" valign="top" charoff="50">0.32–2.05</td>
<td align="center" valign="top" charoff="50">0.66</td>
</tr>
<tr>
<td rowspan="3" align="left" valign="middle" charoff="50">
<italic>
<bold>ADRB2</bold>
</italic>
</td>
<td rowspan="3" align="center" valign="middle" charoff="50">
<italic>rs1042713</italic>
</td>
<td align="center" valign="top" charoff="50">AA</td>
<td align="center" valign="top" charoff="50">104</td>
<td align="center" valign="top" charoff="50">14.23</td>
<td align="center" valign="top" charoff="50">6</td>
<td align="center" valign="top" charoff="50">6.23</td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
<td align="center" valign="top" charoff="50"></td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">AG</td>
<td align="center" valign="top" charoff="50">339</td>
<td align="center" valign="top" charoff="50">46.37</td>
<td align="center" valign="top" charoff="50">33</td>
<td align="center" valign="top" charoff="50">50.77</td>
<td align="center" valign="top" charoff="50">1.68</td>
<td align="center" valign="top" charoff="50">0.68–4.16</td>
<td align="center" valign="top" charoff="50">0.26</td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">GG</td>
<td align="center" valign="top" charoff="50">288</td>
<td align="center" valign="top" charoff="50">39.40</td>
<td align="center" valign="top" charoff="50">26</td>
<td align="center" valign="top" charoff="50">40.00</td>
<td align="center" valign="top" charoff="50">1.61</td>
<td align="center" valign="top" charoff="50">0.64–4.06</td>
<td align="center" valign="top" charoff="50">0.31</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="t3-fn1">
<p>
<sup>a</sup>
Adjusted for age and sex. The participants with prevalent GAD were not included in the analysis.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</floats-group>
</pmc>
</record>

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