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Genome-wide analysis implicates microRNAs and their target genes in the development of bipolar disorder

Identifieur interne : 000880 ( Pmc/Curation ); précédent : 000879; suivant : 000881

Genome-wide analysis implicates microRNAs and their target genes in the development of bipolar disorder

Auteurs : A J Forstner [Allemagne] ; A. Hofmann [Allemagne] ; A. Maaser [Allemagne] ; S. Sumer [Allemagne] ; S. Khudayberdiev [Allemagne] ; T W Mühleisen [Allemagne] ; M. Leber [Allemagne] ; T G Schulze [Allemagne] ; J. Strohmaier [Allemagne] ; F. Degenhardt [Allemagne] ; J. Treutlein [Allemagne] ; M. Mattheisen [Danemark, Allemagne] ; J. Schumacher [Allemagne] ; R. Breuer [Allemagne] ; S. Meier [Allemagne, Danemark] ; S. Herms [Allemagne, Suisse] ; P. Hoffmann [Allemagne, Suisse] ; A. Lacour [Allemagne] ; S H Witt [Allemagne] ; A. Reif [Allemagne] ; B. Müller-Myhsok [Allemagne, Royaume-Uni] ; S. Lucae [Allemagne] ; W. Maier [Allemagne] ; M. Schwarz [Allemagne] ; H. Vedder [Allemagne] ; J. Kammerer-Ciernioch [Allemagne] ; A. Pfennig [Allemagne] ; M. Bauer [Allemagne] ; M. Hautzinger [Allemagne] ; S. Moebus [Allemagne] ; L. Priebe [Allemagne] ; S. Sivalingam [Allemagne] ; A. Verhaert [Allemagne] ; H. Schulz [Allemagne] ; P M Czerski [Pologne] ; J. Hauser [Pologne] ; J. Lissowska [Pologne] ; N. Szeszenia-Dabrowska [Pologne] ; P. Brennan [France] ; J D Mckay [France] ; A. Wright [Australie] ; P B Mitchell [Australie] ; J M Fullerton [Australie] ; P R Schofield [Australie] ; G W Montgomery [Australie] ; S E Medland [Australie] ; S D Gordon [Australie] ; N G Martin [Australie] ; V. Krasnov [Russie] ; A. Chuchalin [Russie] ; G. Babadjanova [Russie] ; G. Pantelejeva [Russie] ; L I Abramova [Russie] ; A S Tiganov [Russie] ; A. Polonikov [Russie] ; E. Khusnutdinova [Russie] ; M. Alda [Canada, République tchèque] ; C. Cruceanu [Canada] ; G A Rouleau [Canada] ; G. Turecki [Canada] ; C. Laprise [Canada] ; F. Rivas [Espagne] ; F. Mayoral [Espagne] ; M. Kogevinas [Espagne] ; M. Grigoroiu-Serbanescu [Roumanie] ; P. Propping [Allemagne] ; T. Becker [Allemagne] ; M. Rietschel [Allemagne] ; S. Cichon [Allemagne, Suisse] ; G. Schratt [Allemagne] ; M M Nöthen [Allemagne]

Source :

RBID : PMC:5068755

Abstract

Bipolar disorder (BD) is a severe and highly heritable neuropsychiatric disorder with a lifetime prevalence of 1%. Molecular genetic studies have identified the first BD susceptibility genes. However, the disease pathways remain largely unknown. Accumulating evidence suggests that microRNAs, a class of small noncoding RNAs, contribute to basic mechanisms underlying brain development and plasticity, suggesting their possible involvement in the pathogenesis of several psychiatric disorders, including BD. In the present study, gene-based analyses were performed for all known autosomal microRNAs using the largest genome-wide association data set of BD to date (9747 patients and 14 278 controls). Associated and brain-expressed microRNAs were then investigated in target gene and pathway analyses. Functional analyses of miR-499 and miR-708 were performed in rat hippocampal neurons. Ninety-eight of the six hundred nine investigated microRNAs showed nominally significant P-values, suggesting that BD-associated microRNAs might be enriched within known microRNA loci. After correction for multiple testing, nine microRNAs showed a significant association with BD. The most promising were miR-499, miR-708 and miR-1908. Target gene and pathway analyses revealed 18 significant canonical pathways, including brain development and neuron projection. For miR-499, four Bonferroni-corrected significant target genes were identified, including the genome-wide risk gene for psychiatric disorder CACNB2. First results of functional analyses in rat hippocampal neurons neither revealed nor excluded a major contribution of miR-499 or miR-708 to dendritic spine morphogenesis. The present results suggest that research is warranted to elucidate the precise involvement of microRNAs and their downstream pathways in BD.


Url:
DOI: 10.1038/tp.2015.159
PubMed: 26556287
PubMed Central: 5068755

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<institution>Institute of Human Genetics, University of Bonn</institution>
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<institution>Department of Genomics, Life and Brain Center, University of Bonn</institution>
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<name sortKey="Khudayberdiev, S" sort="Khudayberdiev, S" uniqKey="Khudayberdiev S" first="S" last="Khudayberdiev">S. Khudayberdiev</name>
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<institution>Institute of Physiological Chemistry, Philipps-University Marburg</institution>
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<name sortKey="Muhleisen, T W" sort="Muhleisen, T W" uniqKey="Muhleisen T" first="T W" last="Mühleisen">T W Mühleisen</name>
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<institution>Institute of Human Genetics, University of Bonn</institution>
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<country xml:lang="fr">Allemagne</country>
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<institution>Department of Genomics, Life and Brain Center, University of Bonn</institution>
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<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<institution>Institute of Neuroscience and Medicine, Research Center Juelich</institution>
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<country xml:lang="fr">Allemagne</country>
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<name sortKey="Leber, M" sort="Leber, M" uniqKey="Leber M" first="M" last="Leber">M. Leber</name>
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<institution>Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn</institution>
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<country xml:lang="fr">Allemagne</country>
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<name sortKey="Schulze, T G" sort="Schulze, T G" uniqKey="Schulze T" first="T G" last="Schulze">T G Schulze</name>
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<institution>Institute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University Munich</institution>
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</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<name sortKey="Strohmaier, J" sort="Strohmaier, J" uniqKey="Strohmaier J" first="J" last="Strohmaier">J. Strohmaier</name>
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<nlm:aff id="aff7">
<institution>Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg</institution>
, Heidelberg,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author>
<name sortKey="Degenhardt, F" sort="Degenhardt, F" uniqKey="Degenhardt F" first="F" last="Degenhardt">F. Degenhardt</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Institute of Human Genetics, University of Bonn</institution>
, Bonn,
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</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<institution>Department of Genomics, Life and Brain Center, University of Bonn</institution>
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<country xml:lang="fr">Allemagne</country>
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<name sortKey="Treutlein, J" sort="Treutlein, J" uniqKey="Treutlein J" first="J" last="Treutlein">J. Treutlein</name>
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<nlm:aff id="aff7">
<institution>Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg</institution>
, Heidelberg,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<name sortKey="Mattheisen, M" sort="Mattheisen, M" uniqKey="Mattheisen M" first="M" last="Mattheisen">M. Mattheisen</name>
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<nlm:aff id="aff8">
<institution>Department of Biomedicine, Aarhus University</institution>
, Aarhus,
<country>Denmark</country>
</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<affiliation wicri:level="1">
<nlm:aff id="aff9">
<institution>Institute for Genomics Mathematics, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<name sortKey="Schumacher, J" sort="Schumacher, J" uniqKey="Schumacher J" first="J" last="Schumacher">J. Schumacher</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Institute of Human Genetics, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Department of Genomics, Life and Brain Center, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<name sortKey="Breuer, R" sort="Breuer, R" uniqKey="Breuer R" first="R" last="Breuer">R. Breuer</name>
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<nlm:aff id="aff7">
<institution>Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg</institution>
, Heidelberg,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<name sortKey="Meier, S" sort="Meier, S" uniqKey="Meier S" first="S" last="Meier">S. Meier</name>
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<nlm:aff id="aff7">
<institution>Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg</institution>
, Heidelberg,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
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<institution>National Center Register-Based Research, Aarhus University</institution>
, Aarhus,
<country>Denmark</country>
</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author>
<name sortKey="Herms, S" sort="Herms, S" uniqKey="Herms S" first="S" last="Herms">S. Herms</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Institute of Human Genetics, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Department of Genomics, Life and Brain Center, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff11">
<institution>Division of Medical Genetics, Department of Biomedicine, University of Basel</institution>
, Basel,
<country>Switzerland</country>
</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Hoffmann, P" sort="Hoffmann, P" uniqKey="Hoffmann P" first="P" last="Hoffmann">P. Hoffmann</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Institute of Human Genetics, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Department of Genomics, Life and Brain Center, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff4">
<institution>Institute of Neuroscience and Medicine, Research Center Juelich</institution>
, Juelich,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff11">
<institution>Division of Medical Genetics, Department of Biomedicine, University of Basel</institution>
, Basel,
<country>Switzerland</country>
</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Lacour, A" sort="Lacour, A" uniqKey="Lacour A" first="A" last="Lacour">A. Lacour</name>
<affiliation wicri:level="1">
<nlm:aff id="aff12">
<institution>German Center for Neurodegenerative Diseases</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Witt, S H" sort="Witt, S H" uniqKey="Witt S" first="S H" last="Witt">S H Witt</name>
<affiliation wicri:level="1">
<nlm:aff id="aff7">
<institution>Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg</institution>
, Heidelberg,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Reif, A" sort="Reif, A" uniqKey="Reif A" first="A" last="Reif">A. Reif</name>
<affiliation wicri:level="1">
<nlm:aff id="aff13">
<institution>Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt am Main</institution>
, Frankfurt,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Muller Myhsok, B" sort="Muller Myhsok, B" uniqKey="Muller Myhsok B" first="B" last="Müller-Myhsok">B. Müller-Myhsok</name>
<affiliation wicri:level="1">
<nlm:aff id="aff14">
<institution>Max Planck Institute of Psychiatry</institution>
, Munich,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff15">
<institution>Munich Cluster for Systems Neurology (SyNergy)</institution>
, Munich,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff16">
<institution>University of Liverpool, Institute of Translational Medicine</institution>
, Liverpool,
<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Lucae, S" sort="Lucae, S" uniqKey="Lucae S" first="S" last="Lucae">S. Lucae</name>
<affiliation wicri:level="1">
<nlm:aff id="aff14">
<institution>Max Planck Institute of Psychiatry</institution>
, Munich,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Maier, W" sort="Maier, W" uniqKey="Maier W" first="W" last="Maier">W. Maier</name>
<affiliation wicri:level="1">
<nlm:aff id="aff17">
<institution>Department of Psychiatry, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Schwarz, M" sort="Schwarz, M" uniqKey="Schwarz M" first="M" last="Schwarz">M. Schwarz</name>
<affiliation wicri:level="1">
<nlm:aff id="aff18">
<institution>Psychiatric Center Nordbaden</institution>
, Wiesloch,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Vedder, H" sort="Vedder, H" uniqKey="Vedder H" first="H" last="Vedder">H. Vedder</name>
<affiliation wicri:level="1">
<nlm:aff id="aff18">
<institution>Psychiatric Center Nordbaden</institution>
, Wiesloch,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Kammerer Ciernioch, J" sort="Kammerer Ciernioch, J" uniqKey="Kammerer Ciernioch J" first="J" last="Kammerer-Ciernioch">J. Kammerer-Ciernioch</name>
<affiliation wicri:level="1">
<nlm:aff id="aff19">
<institution>Center of Psychiatry Weinsberg</institution>
, Weinsberg,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Pfennig, A" sort="Pfennig, A" uniqKey="Pfennig A" first="A" last="Pfennig">A. Pfennig</name>
<affiliation wicri:level="1">
<nlm:aff id="aff20">
<institution>Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus</institution>
, TU Dresden, Dresden,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Bauer, M" sort="Bauer, M" uniqKey="Bauer M" first="M" last="Bauer">M. Bauer</name>
<affiliation wicri:level="1">
<nlm:aff id="aff20">
<institution>Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus</institution>
, TU Dresden, Dresden,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Hautzinger, M" sort="Hautzinger, M" uniqKey="Hautzinger M" first="M" last="Hautzinger">M. Hautzinger</name>
<affiliation wicri:level="1">
<nlm:aff id="aff21">
<institution>Department of Psychology, Clinical Psychology and Psychotherapy, Eberhard Karls University Tübingen</institution>
, Tübingen,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Moebus, S" sort="Moebus, S" uniqKey="Moebus S" first="S" last="Moebus">S. Moebus</name>
<affiliation wicri:level="1">
<nlm:aff id="aff22">
<institution>Institute of Medical Informatics, Biometry and Epidemiology, University Duisburg-Essen</institution>
, Essen,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Priebe, L" sort="Priebe, L" uniqKey="Priebe L" first="L" last="Priebe">L. Priebe</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Institute of Human Genetics, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Department of Genomics, Life and Brain Center, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Sivalingam, S" sort="Sivalingam, S" uniqKey="Sivalingam S" first="S" last="Sivalingam">S. Sivalingam</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Institute of Human Genetics, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Department of Genomics, Life and Brain Center, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Verhaert, A" sort="Verhaert, A" uniqKey="Verhaert A" first="A" last="Verhaert">A. Verhaert</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Institute of Human Genetics, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Department of Genomics, Life and Brain Center, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Schulz, H" sort="Schulz, H" uniqKey="Schulz H" first="H" last="Schulz">H. Schulz</name>
<affiliation wicri:level="1">
<nlm:aff id="aff23">
<institution>Cologne Center for Genomics, University of Cologne</institution>
, Cologne,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Czerski, P M" sort="Czerski, P M" uniqKey="Czerski P" first="P M" last="Czerski">P M Czerski</name>
<affiliation wicri:level="1">
<nlm:aff id="aff24">
<institution>Department of Psychiatry, Laboratory of Psychiatric Genetics, Poznan University of Medical Sciences</institution>
, Poznan,
<country>Poland</country>
</nlm:aff>
<country xml:lang="fr">Pologne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Hauser, J" sort="Hauser, J" uniqKey="Hauser J" first="J" last="Hauser">J. Hauser</name>
<affiliation wicri:level="1">
<nlm:aff id="aff24">
<institution>Department of Psychiatry, Laboratory of Psychiatric Genetics, Poznan University of Medical Sciences</institution>
, Poznan,
<country>Poland</country>
</nlm:aff>
<country xml:lang="fr">Pologne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Lissowska, J" sort="Lissowska, J" uniqKey="Lissowska J" first="J" last="Lissowska">J. Lissowska</name>
<affiliation wicri:level="1">
<nlm:aff id="aff25">
<institution>Department of Cancer Epidemiology and Prevention, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology Warsaw</institution>
, Warsaw,
<country>Poland</country>
</nlm:aff>
<country xml:lang="fr">Pologne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Szeszenia Dabrowska, N" sort="Szeszenia Dabrowska, N" uniqKey="Szeszenia Dabrowska N" first="N" last="Szeszenia-Dabrowska">N. Szeszenia-Dabrowska</name>
<affiliation wicri:level="1">
<nlm:aff id="aff26">
<institution>Department of Epidemiology, Nofer Institute of Occupational Medicine</institution>
, Lodz,
<country>Poland</country>
</nlm:aff>
<country xml:lang="fr">Pologne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Brennan, P" sort="Brennan, P" uniqKey="Brennan P" first="P" last="Brennan">P. Brennan</name>
<affiliation wicri:level="1">
<nlm:aff id="aff27">
<institution>Genetic Epidemiology Group, International Agency for Research on Cancer</institution>
, Lyon,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Mckay, J D" sort="Mckay, J D" uniqKey="Mckay J" first="J D" last="Mckay">J D Mckay</name>
<affiliation wicri:level="1">
<nlm:aff id="aff28">
<institution>Genetic Cancer Susceptibility Group, International Agency for Research on Cancer</institution>
, Lyon,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Wright, A" sort="Wright, A" uniqKey="Wright A" first="A" last="Wright">A. Wright</name>
<affiliation wicri:level="1">
<nlm:aff id="aff29">
<institution>School of Psychiatry, University of New South Wales</institution>
, Randwick, NSW,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff30">
<institution>Black Dog Institute, Prince of Wales Hospital</institution>
, Randwick, NSW,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Mitchell, P B" sort="Mitchell, P B" uniqKey="Mitchell P" first="P B" last="Mitchell">P B Mitchell</name>
<affiliation wicri:level="1">
<nlm:aff id="aff29">
<institution>School of Psychiatry, University of New South Wales</institution>
, Randwick, NSW,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff30">
<institution>Black Dog Institute, Prince of Wales Hospital</institution>
, Randwick, NSW,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Fullerton, J M" sort="Fullerton, J M" uniqKey="Fullerton J" first="J M" last="Fullerton">J M Fullerton</name>
<affiliation wicri:level="1">
<nlm:aff id="aff31">
<institution>Neuroscience Research Australia</institution>
, Sydney, NSW,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff32">
<institution>School of Medical Sciences, Faculty of Medicine, University of New South Wales</institution>
, Sydney, NSW,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Schofield, P R" sort="Schofield, P R" uniqKey="Schofield P" first="P R" last="Schofield">P R Schofield</name>
<affiliation wicri:level="1">
<nlm:aff id="aff31">
<institution>Neuroscience Research Australia</institution>
, Sydney, NSW,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff32">
<institution>School of Medical Sciences, Faculty of Medicine, University of New South Wales</institution>
, Sydney, NSW,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Montgomery, G W" sort="Montgomery, G W" uniqKey="Montgomery G" first="G W" last="Montgomery">G W Montgomery</name>
<affiliation wicri:level="1">
<nlm:aff id="aff33">
<institution>Queensland Institute of Medical Research</institution>
, Brisbane, QLD,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Medland, S E" sort="Medland, S E" uniqKey="Medland S" first="S E" last="Medland">S E Medland</name>
<affiliation wicri:level="1">
<nlm:aff id="aff33">
<institution>Queensland Institute of Medical Research</institution>
, Brisbane, QLD,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Gordon, S D" sort="Gordon, S D" uniqKey="Gordon S" first="S D" last="Gordon">S D Gordon</name>
<affiliation wicri:level="1">
<nlm:aff id="aff33">
<institution>Queensland Institute of Medical Research</institution>
, Brisbane, QLD,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Martin, N G" sort="Martin, N G" uniqKey="Martin N" first="N G" last="Martin">N G Martin</name>
<affiliation wicri:level="1">
<nlm:aff id="aff33">
<institution>Queensland Institute of Medical Research</institution>
, Brisbane, QLD,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Krasnov, V" sort="Krasnov, V" uniqKey="Krasnov V" first="V" last="Krasnov">V. Krasnov</name>
<affiliation wicri:level="1">
<nlm:aff id="aff34">
<institution>Moscow Research Institute of Psychiatry</institution>
, Moscow,
<country>Russian Federation</country>
</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Chuchalin, A" sort="Chuchalin, A" uniqKey="Chuchalin A" first="A" last="Chuchalin">A. Chuchalin</name>
<affiliation wicri:level="1">
<nlm:aff id="aff35">
<institution>Institute of Pulmonology, Russian State Medical University</institution>
, Moscow,
<country>Russian Federation</country>
</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Babadjanova, G" sort="Babadjanova, G" uniqKey="Babadjanova G" first="G" last="Babadjanova">G. Babadjanova</name>
<affiliation wicri:level="1">
<nlm:aff id="aff35">
<institution>Institute of Pulmonology, Russian State Medical University</institution>
, Moscow,
<country>Russian Federation</country>
</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Pantelejeva, G" sort="Pantelejeva, G" uniqKey="Pantelejeva G" first="G" last="Pantelejeva">G. Pantelejeva</name>
<affiliation wicri:level="1">
<nlm:aff id="aff36">
<institution>Russian Academy of Medical Sciences, Mental Health Research Center</institution>
, Moscow,
<country>Russian Federation</country>
</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Abramova, L I" sort="Abramova, L I" uniqKey="Abramova L" first="L I" last="Abramova">L I Abramova</name>
<affiliation wicri:level="1">
<nlm:aff id="aff36">
<institution>Russian Academy of Medical Sciences, Mental Health Research Center</institution>
, Moscow,
<country>Russian Federation</country>
</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Tiganov, A S" sort="Tiganov, A S" uniqKey="Tiganov A" first="A S" last="Tiganov">A S Tiganov</name>
<affiliation wicri:level="1">
<nlm:aff id="aff36">
<institution>Russian Academy of Medical Sciences, Mental Health Research Center</institution>
, Moscow,
<country>Russian Federation</country>
</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Polonikov, A" sort="Polonikov, A" uniqKey="Polonikov A" first="A" last="Polonikov">A. Polonikov</name>
<affiliation wicri:level="1">
<nlm:aff id="aff37">
<institution>Department of Biology, Medical Genetics and Ecology, Kursk State Medical University</institution>
, Kursk,
<country>Russian Federation</country>
</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Khusnutdinova, E" sort="Khusnutdinova, E" uniqKey="Khusnutdinova E" first="E" last="Khusnutdinova">E. Khusnutdinova</name>
<affiliation wicri:level="1">
<nlm:aff id="aff38">
<institution>Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Sciences</institution>
, Ufa,
<country>Russian Federation</country>
</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff39">
<institution>Department of Genetics and Fundamental Medicine, Bashkir State University</institution>
, Ufa,
<country>Russian Federation</country>
</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Alda, M" sort="Alda, M" uniqKey="Alda M" first="M" last="Alda">M. Alda</name>
<affiliation wicri:level="1">
<nlm:aff id="aff40">
<institution>Department of Psychiatry, Dalhousie University</institution>
, Halifax, NS,
<country>Canada</country>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff41">
<institution>National Institute of Mental Health</institution>
, Klecany,
<country>Czech Republic</country>
</nlm:aff>
<country xml:lang="fr">République tchèque</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Cruceanu, C" sort="Cruceanu, C" uniqKey="Cruceanu C" first="C" last="Cruceanu">C. Cruceanu</name>
<affiliation wicri:level="1">
<nlm:aff id="aff42">
<institution>Montreal Neurological Institute, McGill University</institution>
, Montreal, QC,
<country>Canada</country>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff43">
<institution>Department of Human Genetics, McGill University</institution>
, Montreal, QC,
<country>Canada</country>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff44">
<institution>McGill Group for Suicide Studies and Douglas Research Institute</institution>
, Montreal, QC,
<country>Canada</country>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Rouleau, G A" sort="Rouleau, G A" uniqKey="Rouleau G" first="G A" last="Rouleau">G A Rouleau</name>
<affiliation wicri:level="1">
<nlm:aff id="aff42">
<institution>Montreal Neurological Institute, McGill University</institution>
, Montreal, QC,
<country>Canada</country>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Turecki, G" sort="Turecki, G" uniqKey="Turecki G" first="G" last="Turecki">G. Turecki</name>
<affiliation wicri:level="1">
<nlm:aff id="aff43">
<institution>Department of Human Genetics, McGill University</institution>
, Montreal, QC,
<country>Canada</country>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff44">
<institution>McGill Group for Suicide Studies and Douglas Research Institute</institution>
, Montreal, QC,
<country>Canada</country>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff45">
<institution>Department of Psychiatry, McGill University</institution>
, Montreal, QC,
<country>Canada</country>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Laprise, C" sort="Laprise, C" uniqKey="Laprise C" first="C" last="Laprise">C. Laprise</name>
<affiliation wicri:level="1">
<nlm:aff id="aff46">
<institution>Département des sciences fondamentales, Université du Québec à Chicoutimi (UQAC)</institution>
, Chicoutimi, QC,
<country>Canada</country>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Rivas, F" sort="Rivas, F" uniqKey="Rivas F" first="F" last="Rivas">F. Rivas</name>
<affiliation wicri:level="1">
<nlm:aff id="aff47">
<institution>Department of Psychiatry, Hospital Regional Universitario, Biomedical Institute of Malaga</institution>
, Malaga,
<country>Spain</country>
</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Mayoral, F" sort="Mayoral, F" uniqKey="Mayoral F" first="F" last="Mayoral">F. Mayoral</name>
<affiliation wicri:level="1">
<nlm:aff id="aff47">
<institution>Department of Psychiatry, Hospital Regional Universitario, Biomedical Institute of Malaga</institution>
, Malaga,
<country>Spain</country>
</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Kogevinas, M" sort="Kogevinas, M" uniqKey="Kogevinas M" first="M" last="Kogevinas">M. Kogevinas</name>
<affiliation wicri:level="1">
<nlm:aff id="aff48">
<institution>Center for Research in Environmental Epidemiology</institution>
, Barcelona,
<country>Spain</country>
</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Grigoroiu Serbanescu, M" sort="Grigoroiu Serbanescu, M" uniqKey="Grigoroiu Serbanescu M" first="M" last="Grigoroiu-Serbanescu">M. Grigoroiu-Serbanescu</name>
<affiliation wicri:level="1">
<nlm:aff id="aff49">
<institution>Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital</institution>
, Bucharest,
<country>Romania</country>
</nlm:aff>
<country xml:lang="fr">Roumanie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Propping, P" sort="Propping, P" uniqKey="Propping P" first="P" last="Propping">P. Propping</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Institute of Human Genetics, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Becker, T" sort="Becker, T" uniqKey="Becker T" first="T" last="Becker">T. Becker</name>
<affiliation wicri:level="1">
<nlm:aff id="aff5">
<institution>Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff12">
<institution>German Center for Neurodegenerative Diseases</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Rietschel, M" sort="Rietschel, M" uniqKey="Rietschel M" first="M" last="Rietschel">M. Rietschel</name>
<affiliation wicri:level="1">
<nlm:aff id="aff7">
<institution>Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg</institution>
, Heidelberg,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Cichon, S" sort="Cichon, S" uniqKey="Cichon S" first="S" last="Cichon">S. Cichon</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Institute of Human Genetics, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Department of Genomics, Life and Brain Center, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff4">
<institution>Institute of Neuroscience and Medicine, Research Center Juelich</institution>
, Juelich,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff11">
<institution>Division of Medical Genetics, Department of Biomedicine, University of Basel</institution>
, Basel,
<country>Switzerland</country>
</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Schratt, G" sort="Schratt, G" uniqKey="Schratt G" first="G" last="Schratt">G. Schratt</name>
<affiliation wicri:level="1">
<nlm:aff id="aff3">
<institution>Institute of Physiological Chemistry, Philipps-University Marburg</institution>
, Marburg,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Nothen, M M" sort="Nothen, M M" uniqKey="Nothen M" first="M M" last="Nöthen">M M Nöthen</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Institute of Human Genetics, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Department of Genomics, Life and Brain Center, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</titleStmt>
<publicationStmt>
<idno type="wicri:source">PMC</idno>
<idno type="pmid">26556287</idno>
<idno type="pmc">5068755</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5068755</idno>
<idno type="RBID">PMC:5068755</idno>
<idno type="doi">10.1038/tp.2015.159</idno>
<date when="2015">2015</date>
<idno type="wicri:Area/Pmc/Corpus">000881</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000881</idno>
<idno type="wicri:Area/Pmc/Curation">000880</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000880</idno>
</publicationStmt>
<sourceDesc>
<biblStruct>
<analytic>
<title xml:lang="en" level="a" type="main">Genome-wide analysis implicates microRNAs and their target genes in the development of bipolar disorder</title>
<author>
<name sortKey="Forstner, A J" sort="Forstner, A J" uniqKey="Forstner A" first="A J" last="Forstner">A J Forstner</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Institute of Human Genetics, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Department of Genomics, Life and Brain Center, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Hofmann, A" sort="Hofmann, A" uniqKey="Hofmann A" first="A" last="Hofmann">A. Hofmann</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Institute of Human Genetics, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Department of Genomics, Life and Brain Center, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Maaser, A" sort="Maaser, A" uniqKey="Maaser A" first="A" last="Maaser">A. Maaser</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Institute of Human Genetics, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Department of Genomics, Life and Brain Center, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Sumer, S" sort="Sumer, S" uniqKey="Sumer S" first="S" last="Sumer">S. Sumer</name>
<affiliation wicri:level="1">
<nlm:aff id="aff3">
<institution>Institute of Physiological Chemistry, Philipps-University Marburg</institution>
, Marburg,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Khudayberdiev, S" sort="Khudayberdiev, S" uniqKey="Khudayberdiev S" first="S" last="Khudayberdiev">S. Khudayberdiev</name>
<affiliation wicri:level="1">
<nlm:aff id="aff3">
<institution>Institute of Physiological Chemistry, Philipps-University Marburg</institution>
, Marburg,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Muhleisen, T W" sort="Muhleisen, T W" uniqKey="Muhleisen T" first="T W" last="Mühleisen">T W Mühleisen</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Institute of Human Genetics, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Department of Genomics, Life and Brain Center, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff4">
<institution>Institute of Neuroscience and Medicine, Research Center Juelich</institution>
, Juelich,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Leber, M" sort="Leber, M" uniqKey="Leber M" first="M" last="Leber">M. Leber</name>
<affiliation wicri:level="1">
<nlm:aff id="aff5">
<institution>Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Schulze, T G" sort="Schulze, T G" uniqKey="Schulze T" first="T G" last="Schulze">T G Schulze</name>
<affiliation wicri:level="1">
<nlm:aff id="aff6">
<institution>Institute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University Munich</institution>
, Munich,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Strohmaier, J" sort="Strohmaier, J" uniqKey="Strohmaier J" first="J" last="Strohmaier">J. Strohmaier</name>
<affiliation wicri:level="1">
<nlm:aff id="aff7">
<institution>Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg</institution>
, Heidelberg,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Degenhardt, F" sort="Degenhardt, F" uniqKey="Degenhardt F" first="F" last="Degenhardt">F. Degenhardt</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Institute of Human Genetics, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Department of Genomics, Life and Brain Center, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Treutlein, J" sort="Treutlein, J" uniqKey="Treutlein J" first="J" last="Treutlein">J. Treutlein</name>
<affiliation wicri:level="1">
<nlm:aff id="aff7">
<institution>Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg</institution>
, Heidelberg,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Mattheisen, M" sort="Mattheisen, M" uniqKey="Mattheisen M" first="M" last="Mattheisen">M. Mattheisen</name>
<affiliation wicri:level="1">
<nlm:aff id="aff8">
<institution>Department of Biomedicine, Aarhus University</institution>
, Aarhus,
<country>Denmark</country>
</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff9">
<institution>Institute for Genomics Mathematics, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Schumacher, J" sort="Schumacher, J" uniqKey="Schumacher J" first="J" last="Schumacher">J. Schumacher</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Institute of Human Genetics, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Department of Genomics, Life and Brain Center, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Breuer, R" sort="Breuer, R" uniqKey="Breuer R" first="R" last="Breuer">R. Breuer</name>
<affiliation wicri:level="1">
<nlm:aff id="aff7">
<institution>Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg</institution>
, Heidelberg,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Meier, S" sort="Meier, S" uniqKey="Meier S" first="S" last="Meier">S. Meier</name>
<affiliation wicri:level="1">
<nlm:aff id="aff7">
<institution>Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg</institution>
, Heidelberg,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff10">
<institution>National Center Register-Based Research, Aarhus University</institution>
, Aarhus,
<country>Denmark</country>
</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Herms, S" sort="Herms, S" uniqKey="Herms S" first="S" last="Herms">S. Herms</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Institute of Human Genetics, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Department of Genomics, Life and Brain Center, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff11">
<institution>Division of Medical Genetics, Department of Biomedicine, University of Basel</institution>
, Basel,
<country>Switzerland</country>
</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Hoffmann, P" sort="Hoffmann, P" uniqKey="Hoffmann P" first="P" last="Hoffmann">P. Hoffmann</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Institute of Human Genetics, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Department of Genomics, Life and Brain Center, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff4">
<institution>Institute of Neuroscience and Medicine, Research Center Juelich</institution>
, Juelich,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff11">
<institution>Division of Medical Genetics, Department of Biomedicine, University of Basel</institution>
, Basel,
<country>Switzerland</country>
</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Lacour, A" sort="Lacour, A" uniqKey="Lacour A" first="A" last="Lacour">A. Lacour</name>
<affiliation wicri:level="1">
<nlm:aff id="aff12">
<institution>German Center for Neurodegenerative Diseases</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Witt, S H" sort="Witt, S H" uniqKey="Witt S" first="S H" last="Witt">S H Witt</name>
<affiliation wicri:level="1">
<nlm:aff id="aff7">
<institution>Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg</institution>
, Heidelberg,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Reif, A" sort="Reif, A" uniqKey="Reif A" first="A" last="Reif">A. Reif</name>
<affiliation wicri:level="1">
<nlm:aff id="aff13">
<institution>Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt am Main</institution>
, Frankfurt,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Muller Myhsok, B" sort="Muller Myhsok, B" uniqKey="Muller Myhsok B" first="B" last="Müller-Myhsok">B. Müller-Myhsok</name>
<affiliation wicri:level="1">
<nlm:aff id="aff14">
<institution>Max Planck Institute of Psychiatry</institution>
, Munich,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff15">
<institution>Munich Cluster for Systems Neurology (SyNergy)</institution>
, Munich,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff16">
<institution>University of Liverpool, Institute of Translational Medicine</institution>
, Liverpool,
<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Lucae, S" sort="Lucae, S" uniqKey="Lucae S" first="S" last="Lucae">S. Lucae</name>
<affiliation wicri:level="1">
<nlm:aff id="aff14">
<institution>Max Planck Institute of Psychiatry</institution>
, Munich,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Maier, W" sort="Maier, W" uniqKey="Maier W" first="W" last="Maier">W. Maier</name>
<affiliation wicri:level="1">
<nlm:aff id="aff17">
<institution>Department of Psychiatry, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Schwarz, M" sort="Schwarz, M" uniqKey="Schwarz M" first="M" last="Schwarz">M. Schwarz</name>
<affiliation wicri:level="1">
<nlm:aff id="aff18">
<institution>Psychiatric Center Nordbaden</institution>
, Wiesloch,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Vedder, H" sort="Vedder, H" uniqKey="Vedder H" first="H" last="Vedder">H. Vedder</name>
<affiliation wicri:level="1">
<nlm:aff id="aff18">
<institution>Psychiatric Center Nordbaden</institution>
, Wiesloch,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Kammerer Ciernioch, J" sort="Kammerer Ciernioch, J" uniqKey="Kammerer Ciernioch J" first="J" last="Kammerer-Ciernioch">J. Kammerer-Ciernioch</name>
<affiliation wicri:level="1">
<nlm:aff id="aff19">
<institution>Center of Psychiatry Weinsberg</institution>
, Weinsberg,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Pfennig, A" sort="Pfennig, A" uniqKey="Pfennig A" first="A" last="Pfennig">A. Pfennig</name>
<affiliation wicri:level="1">
<nlm:aff id="aff20">
<institution>Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus</institution>
, TU Dresden, Dresden,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Bauer, M" sort="Bauer, M" uniqKey="Bauer M" first="M" last="Bauer">M. Bauer</name>
<affiliation wicri:level="1">
<nlm:aff id="aff20">
<institution>Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus</institution>
, TU Dresden, Dresden,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Hautzinger, M" sort="Hautzinger, M" uniqKey="Hautzinger M" first="M" last="Hautzinger">M. Hautzinger</name>
<affiliation wicri:level="1">
<nlm:aff id="aff21">
<institution>Department of Psychology, Clinical Psychology and Psychotherapy, Eberhard Karls University Tübingen</institution>
, Tübingen,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Moebus, S" sort="Moebus, S" uniqKey="Moebus S" first="S" last="Moebus">S. Moebus</name>
<affiliation wicri:level="1">
<nlm:aff id="aff22">
<institution>Institute of Medical Informatics, Biometry and Epidemiology, University Duisburg-Essen</institution>
, Essen,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Priebe, L" sort="Priebe, L" uniqKey="Priebe L" first="L" last="Priebe">L. Priebe</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Institute of Human Genetics, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Department of Genomics, Life and Brain Center, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Sivalingam, S" sort="Sivalingam, S" uniqKey="Sivalingam S" first="S" last="Sivalingam">S. Sivalingam</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Institute of Human Genetics, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Department of Genomics, Life and Brain Center, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Verhaert, A" sort="Verhaert, A" uniqKey="Verhaert A" first="A" last="Verhaert">A. Verhaert</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Institute of Human Genetics, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Department of Genomics, Life and Brain Center, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Schulz, H" sort="Schulz, H" uniqKey="Schulz H" first="H" last="Schulz">H. Schulz</name>
<affiliation wicri:level="1">
<nlm:aff id="aff23">
<institution>Cologne Center for Genomics, University of Cologne</institution>
, Cologne,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Czerski, P M" sort="Czerski, P M" uniqKey="Czerski P" first="P M" last="Czerski">P M Czerski</name>
<affiliation wicri:level="1">
<nlm:aff id="aff24">
<institution>Department of Psychiatry, Laboratory of Psychiatric Genetics, Poznan University of Medical Sciences</institution>
, Poznan,
<country>Poland</country>
</nlm:aff>
<country xml:lang="fr">Pologne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Hauser, J" sort="Hauser, J" uniqKey="Hauser J" first="J" last="Hauser">J. Hauser</name>
<affiliation wicri:level="1">
<nlm:aff id="aff24">
<institution>Department of Psychiatry, Laboratory of Psychiatric Genetics, Poznan University of Medical Sciences</institution>
, Poznan,
<country>Poland</country>
</nlm:aff>
<country xml:lang="fr">Pologne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Lissowska, J" sort="Lissowska, J" uniqKey="Lissowska J" first="J" last="Lissowska">J. Lissowska</name>
<affiliation wicri:level="1">
<nlm:aff id="aff25">
<institution>Department of Cancer Epidemiology and Prevention, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology Warsaw</institution>
, Warsaw,
<country>Poland</country>
</nlm:aff>
<country xml:lang="fr">Pologne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Szeszenia Dabrowska, N" sort="Szeszenia Dabrowska, N" uniqKey="Szeszenia Dabrowska N" first="N" last="Szeszenia-Dabrowska">N. Szeszenia-Dabrowska</name>
<affiliation wicri:level="1">
<nlm:aff id="aff26">
<institution>Department of Epidemiology, Nofer Institute of Occupational Medicine</institution>
, Lodz,
<country>Poland</country>
</nlm:aff>
<country xml:lang="fr">Pologne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Brennan, P" sort="Brennan, P" uniqKey="Brennan P" first="P" last="Brennan">P. Brennan</name>
<affiliation wicri:level="1">
<nlm:aff id="aff27">
<institution>Genetic Epidemiology Group, International Agency for Research on Cancer</institution>
, Lyon,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Mckay, J D" sort="Mckay, J D" uniqKey="Mckay J" first="J D" last="Mckay">J D Mckay</name>
<affiliation wicri:level="1">
<nlm:aff id="aff28">
<institution>Genetic Cancer Susceptibility Group, International Agency for Research on Cancer</institution>
, Lyon,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Wright, A" sort="Wright, A" uniqKey="Wright A" first="A" last="Wright">A. Wright</name>
<affiliation wicri:level="1">
<nlm:aff id="aff29">
<institution>School of Psychiatry, University of New South Wales</institution>
, Randwick, NSW,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff30">
<institution>Black Dog Institute, Prince of Wales Hospital</institution>
, Randwick, NSW,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Mitchell, P B" sort="Mitchell, P B" uniqKey="Mitchell P" first="P B" last="Mitchell">P B Mitchell</name>
<affiliation wicri:level="1">
<nlm:aff id="aff29">
<institution>School of Psychiatry, University of New South Wales</institution>
, Randwick, NSW,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff30">
<institution>Black Dog Institute, Prince of Wales Hospital</institution>
, Randwick, NSW,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Fullerton, J M" sort="Fullerton, J M" uniqKey="Fullerton J" first="J M" last="Fullerton">J M Fullerton</name>
<affiliation wicri:level="1">
<nlm:aff id="aff31">
<institution>Neuroscience Research Australia</institution>
, Sydney, NSW,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff32">
<institution>School of Medical Sciences, Faculty of Medicine, University of New South Wales</institution>
, Sydney, NSW,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Schofield, P R" sort="Schofield, P R" uniqKey="Schofield P" first="P R" last="Schofield">P R Schofield</name>
<affiliation wicri:level="1">
<nlm:aff id="aff31">
<institution>Neuroscience Research Australia</institution>
, Sydney, NSW,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff32">
<institution>School of Medical Sciences, Faculty of Medicine, University of New South Wales</institution>
, Sydney, NSW,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Montgomery, G W" sort="Montgomery, G W" uniqKey="Montgomery G" first="G W" last="Montgomery">G W Montgomery</name>
<affiliation wicri:level="1">
<nlm:aff id="aff33">
<institution>Queensland Institute of Medical Research</institution>
, Brisbane, QLD,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Medland, S E" sort="Medland, S E" uniqKey="Medland S" first="S E" last="Medland">S E Medland</name>
<affiliation wicri:level="1">
<nlm:aff id="aff33">
<institution>Queensland Institute of Medical Research</institution>
, Brisbane, QLD,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Gordon, S D" sort="Gordon, S D" uniqKey="Gordon S" first="S D" last="Gordon">S D Gordon</name>
<affiliation wicri:level="1">
<nlm:aff id="aff33">
<institution>Queensland Institute of Medical Research</institution>
, Brisbane, QLD,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Martin, N G" sort="Martin, N G" uniqKey="Martin N" first="N G" last="Martin">N G Martin</name>
<affiliation wicri:level="1">
<nlm:aff id="aff33">
<institution>Queensland Institute of Medical Research</institution>
, Brisbane, QLD,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Krasnov, V" sort="Krasnov, V" uniqKey="Krasnov V" first="V" last="Krasnov">V. Krasnov</name>
<affiliation wicri:level="1">
<nlm:aff id="aff34">
<institution>Moscow Research Institute of Psychiatry</institution>
, Moscow,
<country>Russian Federation</country>
</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Chuchalin, A" sort="Chuchalin, A" uniqKey="Chuchalin A" first="A" last="Chuchalin">A. Chuchalin</name>
<affiliation wicri:level="1">
<nlm:aff id="aff35">
<institution>Institute of Pulmonology, Russian State Medical University</institution>
, Moscow,
<country>Russian Federation</country>
</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Babadjanova, G" sort="Babadjanova, G" uniqKey="Babadjanova G" first="G" last="Babadjanova">G. Babadjanova</name>
<affiliation wicri:level="1">
<nlm:aff id="aff35">
<institution>Institute of Pulmonology, Russian State Medical University</institution>
, Moscow,
<country>Russian Federation</country>
</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Pantelejeva, G" sort="Pantelejeva, G" uniqKey="Pantelejeva G" first="G" last="Pantelejeva">G. Pantelejeva</name>
<affiliation wicri:level="1">
<nlm:aff id="aff36">
<institution>Russian Academy of Medical Sciences, Mental Health Research Center</institution>
, Moscow,
<country>Russian Federation</country>
</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Abramova, L I" sort="Abramova, L I" uniqKey="Abramova L" first="L I" last="Abramova">L I Abramova</name>
<affiliation wicri:level="1">
<nlm:aff id="aff36">
<institution>Russian Academy of Medical Sciences, Mental Health Research Center</institution>
, Moscow,
<country>Russian Federation</country>
</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Tiganov, A S" sort="Tiganov, A S" uniqKey="Tiganov A" first="A S" last="Tiganov">A S Tiganov</name>
<affiliation wicri:level="1">
<nlm:aff id="aff36">
<institution>Russian Academy of Medical Sciences, Mental Health Research Center</institution>
, Moscow,
<country>Russian Federation</country>
</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Polonikov, A" sort="Polonikov, A" uniqKey="Polonikov A" first="A" last="Polonikov">A. Polonikov</name>
<affiliation wicri:level="1">
<nlm:aff id="aff37">
<institution>Department of Biology, Medical Genetics and Ecology, Kursk State Medical University</institution>
, Kursk,
<country>Russian Federation</country>
</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Khusnutdinova, E" sort="Khusnutdinova, E" uniqKey="Khusnutdinova E" first="E" last="Khusnutdinova">E. Khusnutdinova</name>
<affiliation wicri:level="1">
<nlm:aff id="aff38">
<institution>Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Sciences</institution>
, Ufa,
<country>Russian Federation</country>
</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff39">
<institution>Department of Genetics and Fundamental Medicine, Bashkir State University</institution>
, Ufa,
<country>Russian Federation</country>
</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Alda, M" sort="Alda, M" uniqKey="Alda M" first="M" last="Alda">M. Alda</name>
<affiliation wicri:level="1">
<nlm:aff id="aff40">
<institution>Department of Psychiatry, Dalhousie University</institution>
, Halifax, NS,
<country>Canada</country>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff41">
<institution>National Institute of Mental Health</institution>
, Klecany,
<country>Czech Republic</country>
</nlm:aff>
<country xml:lang="fr">République tchèque</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Cruceanu, C" sort="Cruceanu, C" uniqKey="Cruceanu C" first="C" last="Cruceanu">C. Cruceanu</name>
<affiliation wicri:level="1">
<nlm:aff id="aff42">
<institution>Montreal Neurological Institute, McGill University</institution>
, Montreal, QC,
<country>Canada</country>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff43">
<institution>Department of Human Genetics, McGill University</institution>
, Montreal, QC,
<country>Canada</country>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff44">
<institution>McGill Group for Suicide Studies and Douglas Research Institute</institution>
, Montreal, QC,
<country>Canada</country>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Rouleau, G A" sort="Rouleau, G A" uniqKey="Rouleau G" first="G A" last="Rouleau">G A Rouleau</name>
<affiliation wicri:level="1">
<nlm:aff id="aff42">
<institution>Montreal Neurological Institute, McGill University</institution>
, Montreal, QC,
<country>Canada</country>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Turecki, G" sort="Turecki, G" uniqKey="Turecki G" first="G" last="Turecki">G. Turecki</name>
<affiliation wicri:level="1">
<nlm:aff id="aff43">
<institution>Department of Human Genetics, McGill University</institution>
, Montreal, QC,
<country>Canada</country>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff44">
<institution>McGill Group for Suicide Studies and Douglas Research Institute</institution>
, Montreal, QC,
<country>Canada</country>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff45">
<institution>Department of Psychiatry, McGill University</institution>
, Montreal, QC,
<country>Canada</country>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Laprise, C" sort="Laprise, C" uniqKey="Laprise C" first="C" last="Laprise">C. Laprise</name>
<affiliation wicri:level="1">
<nlm:aff id="aff46">
<institution>Département des sciences fondamentales, Université du Québec à Chicoutimi (UQAC)</institution>
, Chicoutimi, QC,
<country>Canada</country>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Rivas, F" sort="Rivas, F" uniqKey="Rivas F" first="F" last="Rivas">F. Rivas</name>
<affiliation wicri:level="1">
<nlm:aff id="aff47">
<institution>Department of Psychiatry, Hospital Regional Universitario, Biomedical Institute of Malaga</institution>
, Malaga,
<country>Spain</country>
</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Mayoral, F" sort="Mayoral, F" uniqKey="Mayoral F" first="F" last="Mayoral">F. Mayoral</name>
<affiliation wicri:level="1">
<nlm:aff id="aff47">
<institution>Department of Psychiatry, Hospital Regional Universitario, Biomedical Institute of Malaga</institution>
, Malaga,
<country>Spain</country>
</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Kogevinas, M" sort="Kogevinas, M" uniqKey="Kogevinas M" first="M" last="Kogevinas">M. Kogevinas</name>
<affiliation wicri:level="1">
<nlm:aff id="aff48">
<institution>Center for Research in Environmental Epidemiology</institution>
, Barcelona,
<country>Spain</country>
</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Grigoroiu Serbanescu, M" sort="Grigoroiu Serbanescu, M" uniqKey="Grigoroiu Serbanescu M" first="M" last="Grigoroiu-Serbanescu">M. Grigoroiu-Serbanescu</name>
<affiliation wicri:level="1">
<nlm:aff id="aff49">
<institution>Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital</institution>
, Bucharest,
<country>Romania</country>
</nlm:aff>
<country xml:lang="fr">Roumanie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Propping, P" sort="Propping, P" uniqKey="Propping P" first="P" last="Propping">P. Propping</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Institute of Human Genetics, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Becker, T" sort="Becker, T" uniqKey="Becker T" first="T" last="Becker">T. Becker</name>
<affiliation wicri:level="1">
<nlm:aff id="aff5">
<institution>Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff12">
<institution>German Center for Neurodegenerative Diseases</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Rietschel, M" sort="Rietschel, M" uniqKey="Rietschel M" first="M" last="Rietschel">M. Rietschel</name>
<affiliation wicri:level="1">
<nlm:aff id="aff7">
<institution>Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg</institution>
, Heidelberg,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Cichon, S" sort="Cichon, S" uniqKey="Cichon S" first="S" last="Cichon">S. Cichon</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Institute of Human Genetics, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Department of Genomics, Life and Brain Center, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff4">
<institution>Institute of Neuroscience and Medicine, Research Center Juelich</institution>
, Juelich,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff11">
<institution>Division of Medical Genetics, Department of Biomedicine, University of Basel</institution>
, Basel,
<country>Switzerland</country>
</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Schratt, G" sort="Schratt, G" uniqKey="Schratt G" first="G" last="Schratt">G. Schratt</name>
<affiliation wicri:level="1">
<nlm:aff id="aff3">
<institution>Institute of Physiological Chemistry, Philipps-University Marburg</institution>
, Marburg,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Nothen, M M" sort="Nothen, M M" uniqKey="Nothen M" first="M M" last="Nöthen">M M Nöthen</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Institute of Human Genetics, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Department of Genomics, Life and Brain Center, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Translational Psychiatry</title>
<idno type="eISSN">2158-3188</idno>
<imprint>
<date when="2015">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p>Bipolar disorder (BD) is a severe and highly heritable neuropsychiatric disorder with a lifetime prevalence of 1%. Molecular genetic studies have identified the first BD susceptibility genes. However, the disease pathways remain largely unknown. Accumulating evidence suggests that microRNAs, a class of small noncoding RNAs, contribute to basic mechanisms underlying brain development and plasticity, suggesting their possible involvement in the pathogenesis of several psychiatric disorders, including BD. In the present study, gene-based analyses were performed for all known autosomal microRNAs using the largest genome-wide association data set of BD to date (9747 patients and 14 278 controls). Associated and brain-expressed microRNAs were then investigated in target gene and pathway analyses. Functional analyses of
<italic>miR-499</italic>
and
<italic>miR-708</italic>
were performed in rat hippocampal neurons. Ninety-eight of the six hundred nine investigated microRNAs showed nominally significant
<italic>P</italic>
-values, suggesting that BD-associated microRNAs might be enriched within known microRNA loci. After correction for multiple testing, nine microRNAs showed a significant association with BD. The most promising were
<italic>miR-499</italic>
,
<italic>miR-708</italic>
and
<italic>miR-1908</italic>
. Target gene and pathway analyses revealed 18 significant canonical pathways, including brain development and neuron projection. For
<italic>miR-499</italic>
, four Bonferroni-corrected significant target genes were identified, including the genome-wide risk gene for psychiatric disorder
<italic>CACNB2</italic>
. First results of functional analyses in rat hippocampal neurons neither revealed nor excluded a major contribution of
<italic>miR-499</italic>
or
<italic>miR-708</italic>
to dendritic spine morphogenesis. The present results suggest that research is warranted to elucidate the precise involvement of microRNAs and their downstream pathways in BD.</p>
</div>
</front>
<back>
<div1 type="bibliography">
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</div1>
</back>
</TEI>
<pmc article-type="research-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Transl Psychiatry</journal-id>
<journal-id journal-id-type="iso-abbrev">Transl Psychiatry</journal-id>
<journal-title-group>
<journal-title>Translational Psychiatry</journal-title>
</journal-title-group>
<issn pub-type="epub">2158-3188</issn>
<publisher>
<publisher-name>Nature Publishing Group</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">26556287</article-id>
<article-id pub-id-type="pmc">5068755</article-id>
<article-id pub-id-type="pii">tp2015159</article-id>
<article-id pub-id-type="doi">10.1038/tp.2015.159</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Original Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Genome-wide analysis implicates microRNAs and their target genes in the development of bipolar disorder</article-title>
<alt-title alt-title-type="running">microRNAs in bipolar disorder</alt-title>
</title-group>
<contrib-group>
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<surname>Forstner</surname>
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<sup>50</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hofmann</surname>
<given-names>A</given-names>
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<sup>50</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
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<given-names>J</given-names>
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<name>
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<given-names>M</given-names>
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<contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-8442-493X</contrib-id>
</contrib>
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<surname>Schumacher</surname>
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<name>
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<given-names>R</given-names>
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<contrib contrib-type="author">
<name>
<surname>Meier</surname>
<given-names>S</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Herms</surname>
<given-names>S</given-names>
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<contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-2786-8200</contrib-id>
</contrib>
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<xref ref-type="aff" rid="aff11">11</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lacour</surname>
<given-names>A</given-names>
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<contrib-id contrib-id-type="orcid">http://orcid.org/0000-0003-2692-2583</contrib-id>
</contrib>
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</contrib>
<contrib contrib-type="author">
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<surname>Reif</surname>
<given-names>A</given-names>
</name>
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<contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-0992-634X</contrib-id>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Müller-Myhsok</surname>
<given-names>B</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Lucae</surname>
<given-names>S</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Maier</surname>
<given-names>W</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Schwarz</surname>
<given-names>M</given-names>
</name>
<xref ref-type="aff" rid="aff18">18</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Vedder</surname>
<given-names>H</given-names>
</name>
<xref ref-type="aff" rid="aff18">18</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kammerer-Ciernioch</surname>
<given-names>J</given-names>
</name>
<xref ref-type="aff" rid="aff19">19</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Pfennig</surname>
<given-names>A</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Bauer</surname>
<given-names>M</given-names>
</name>
<xref ref-type="aff" rid="aff20">20</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hautzinger</surname>
<given-names>M</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Moebus</surname>
<given-names>S</given-names>
</name>
<xref ref-type="aff" rid="aff22">22</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Priebe</surname>
<given-names>L</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Sivalingam</surname>
<given-names>S</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Verhaert</surname>
<given-names>A</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Schulz</surname>
<given-names>H</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Czerski</surname>
<given-names>P M</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Hauser</surname>
<given-names>J</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Lissowska</surname>
<given-names>J</given-names>
</name>
<xref ref-type="aff" rid="aff25">25</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Szeszenia-Dabrowska</surname>
<given-names>N</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Brennan</surname>
<given-names>P</given-names>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>McKay</surname>
<given-names>J D</given-names>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Wright</surname>
<given-names>A</given-names>
</name>
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</contrib>
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<name>
<surname>Mitchell</surname>
<given-names>P B</given-names>
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</contrib>
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<name>
<surname>Fullerton</surname>
<given-names>J M</given-names>
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<name>
<surname>Schofield</surname>
<given-names>P R</given-names>
</name>
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<xref ref-type="aff" rid="aff32">32</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Montgomery</surname>
<given-names>G W</given-names>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Medland</surname>
<given-names>S E</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Gordon</surname>
<given-names>S D</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Martin</surname>
<given-names>N G</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Krasnov</surname>
<given-names>V</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Chuchalin</surname>
<given-names>A</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Babadjanova</surname>
<given-names>G</given-names>
</name>
<xref ref-type="aff" rid="aff35">35</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Pantelejeva</surname>
<given-names>G</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Abramova</surname>
<given-names>L I</given-names>
</name>
<xref ref-type="aff" rid="aff36">36</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Tiganov</surname>
<given-names>A S</given-names>
</name>
<xref ref-type="aff" rid="aff36">36</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Polonikov</surname>
<given-names>A</given-names>
</name>
<xref ref-type="aff" rid="aff37">37</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Khusnutdinova</surname>
<given-names>E</given-names>
</name>
<xref ref-type="aff" rid="aff38">38</xref>
<xref ref-type="aff" rid="aff39">39</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Alda</surname>
<given-names>M</given-names>
</name>
<xref ref-type="aff" rid="aff40">40</xref>
<xref ref-type="aff" rid="aff41">41</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Cruceanu</surname>
<given-names>C</given-names>
</name>
<xref ref-type="aff" rid="aff42">42</xref>
<xref ref-type="aff" rid="aff43">43</xref>
<xref ref-type="aff" rid="aff44">44</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Rouleau</surname>
<given-names>G A</given-names>
</name>
<xref ref-type="aff" rid="aff42">42</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Turecki</surname>
<given-names>G</given-names>
</name>
<xref ref-type="aff" rid="aff43">43</xref>
<xref ref-type="aff" rid="aff44">44</xref>
<xref ref-type="aff" rid="aff45">45</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Laprise</surname>
<given-names>C</given-names>
</name>
<xref ref-type="aff" rid="aff46">46</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Rivas</surname>
<given-names>F</given-names>
</name>
<xref ref-type="aff" rid="aff47">47</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Mayoral</surname>
<given-names>F</given-names>
</name>
<xref ref-type="aff" rid="aff47">47</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kogevinas</surname>
<given-names>M</given-names>
</name>
<xref ref-type="aff" rid="aff48">48</xref>
<contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-9605-0461</contrib-id>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Grigoroiu-Serbanescu</surname>
<given-names>M</given-names>
</name>
<xref ref-type="aff" rid="aff49">49</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Propping</surname>
<given-names>P</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Becker</surname>
<given-names>T</given-names>
</name>
<xref ref-type="aff" rid="aff5">5</xref>
<xref ref-type="aff" rid="aff12">12</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Rietschel</surname>
<given-names>M</given-names>
</name>
<xref ref-type="aff" rid="aff7">7</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Cichon</surname>
<given-names>S</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="aff" rid="aff2">2</xref>
<xref ref-type="aff" rid="aff4">4</xref>
<xref ref-type="aff" rid="aff11">11</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Schratt</surname>
<given-names>G</given-names>
</name>
<xref ref-type="aff" rid="aff3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Nöthen</surname>
<given-names>M M</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="aff" rid="aff2">2</xref>
<xref ref-type="corresp" rid="caf1">*</xref>
</contrib>
<aff id="aff1">
<label>1</label>
<institution>Institute of Human Genetics, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</aff>
<aff id="aff2">
<label>2</label>
<institution>Department of Genomics, Life and Brain Center, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</aff>
<aff id="aff3">
<label>3</label>
<institution>Institute of Physiological Chemistry, Philipps-University Marburg</institution>
, Marburg,
<country>Germany</country>
</aff>
<aff id="aff4">
<label>4</label>
<institution>Institute of Neuroscience and Medicine, Research Center Juelich</institution>
, Juelich,
<country>Germany</country>
</aff>
<aff id="aff5">
<label>5</label>
<institution>Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</aff>
<aff id="aff6">
<label>6</label>
<institution>Institute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University Munich</institution>
, Munich,
<country>Germany</country>
</aff>
<aff id="aff7">
<label>7</label>
<institution>Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg</institution>
, Heidelberg,
<country>Germany</country>
</aff>
<aff id="aff8">
<label>8</label>
<institution>Department of Biomedicine, Aarhus University</institution>
, Aarhus,
<country>Denmark</country>
</aff>
<aff id="aff9">
<label>9</label>
<institution>Institute for Genomics Mathematics, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</aff>
<aff id="aff10">
<label>10</label>
<institution>National Center Register-Based Research, Aarhus University</institution>
, Aarhus,
<country>Denmark</country>
</aff>
<aff id="aff11">
<label>11</label>
<institution>Division of Medical Genetics, Department of Biomedicine, University of Basel</institution>
, Basel,
<country>Switzerland</country>
</aff>
<aff id="aff12">
<label>12</label>
<institution>German Center for Neurodegenerative Diseases</institution>
, Bonn,
<country>Germany</country>
</aff>
<aff id="aff13">
<label>13</label>
<institution>Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt am Main</institution>
, Frankfurt,
<country>Germany</country>
</aff>
<aff id="aff14">
<label>14</label>
<institution>Max Planck Institute of Psychiatry</institution>
, Munich,
<country>Germany</country>
</aff>
<aff id="aff15">
<label>15</label>
<institution>Munich Cluster for Systems Neurology (SyNergy)</institution>
, Munich,
<country>Germany</country>
</aff>
<aff id="aff16">
<label>16</label>
<institution>University of Liverpool, Institute of Translational Medicine</institution>
, Liverpool,
<country>UK</country>
</aff>
<aff id="aff17">
<label>17</label>
<institution>Department of Psychiatry, University of Bonn</institution>
, Bonn,
<country>Germany</country>
</aff>
<aff id="aff18">
<label>18</label>
<institution>Psychiatric Center Nordbaden</institution>
, Wiesloch,
<country>Germany</country>
</aff>
<aff id="aff19">
<label>19</label>
<institution>Center of Psychiatry Weinsberg</institution>
, Weinsberg,
<country>Germany</country>
</aff>
<aff id="aff20">
<label>20</label>
<institution>Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus</institution>
, TU Dresden, Dresden,
<country>Germany</country>
</aff>
<aff id="aff21">
<label>21</label>
<institution>Department of Psychology, Clinical Psychology and Psychotherapy, Eberhard Karls University Tübingen</institution>
, Tübingen,
<country>Germany</country>
</aff>
<aff id="aff22">
<label>22</label>
<institution>Institute of Medical Informatics, Biometry and Epidemiology, University Duisburg-Essen</institution>
, Essen,
<country>Germany</country>
</aff>
<aff id="aff23">
<label>23</label>
<institution>Cologne Center for Genomics, University of Cologne</institution>
, Cologne,
<country>Germany</country>
</aff>
<aff id="aff24">
<label>24</label>
<institution>Department of Psychiatry, Laboratory of Psychiatric Genetics, Poznan University of Medical Sciences</institution>
, Poznan,
<country>Poland</country>
</aff>
<aff id="aff25">
<label>25</label>
<institution>Department of Cancer Epidemiology and Prevention, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology Warsaw</institution>
, Warsaw,
<country>Poland</country>
</aff>
<aff id="aff26">
<label>26</label>
<institution>Department of Epidemiology, Nofer Institute of Occupational Medicine</institution>
, Lodz,
<country>Poland</country>
</aff>
<aff id="aff27">
<label>27</label>
<institution>Genetic Epidemiology Group, International Agency for Research on Cancer</institution>
, Lyon,
<country>France</country>
</aff>
<aff id="aff28">
<label>28</label>
<institution>Genetic Cancer Susceptibility Group, International Agency for Research on Cancer</institution>
, Lyon,
<country>France</country>
</aff>
<aff id="aff29">
<label>29</label>
<institution>School of Psychiatry, University of New South Wales</institution>
, Randwick, NSW,
<country>Australia</country>
</aff>
<aff id="aff30">
<label>30</label>
<institution>Black Dog Institute, Prince of Wales Hospital</institution>
, Randwick, NSW,
<country>Australia</country>
</aff>
<aff id="aff31">
<label>31</label>
<institution>Neuroscience Research Australia</institution>
, Sydney, NSW,
<country>Australia</country>
</aff>
<aff id="aff32">
<label>32</label>
<institution>School of Medical Sciences, Faculty of Medicine, University of New South Wales</institution>
, Sydney, NSW,
<country>Australia</country>
</aff>
<aff id="aff33">
<label>33</label>
<institution>Queensland Institute of Medical Research</institution>
, Brisbane, QLD,
<country>Australia</country>
</aff>
<aff id="aff34">
<label>34</label>
<institution>Moscow Research Institute of Psychiatry</institution>
, Moscow,
<country>Russian Federation</country>
</aff>
<aff id="aff35">
<label>35</label>
<institution>Institute of Pulmonology, Russian State Medical University</institution>
, Moscow,
<country>Russian Federation</country>
</aff>
<aff id="aff36">
<label>36</label>
<institution>Russian Academy of Medical Sciences, Mental Health Research Center</institution>
, Moscow,
<country>Russian Federation</country>
</aff>
<aff id="aff37">
<label>37</label>
<institution>Department of Biology, Medical Genetics and Ecology, Kursk State Medical University</institution>
, Kursk,
<country>Russian Federation</country>
</aff>
<aff id="aff38">
<label>38</label>
<institution>Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Sciences</institution>
, Ufa,
<country>Russian Federation</country>
</aff>
<aff id="aff39">
<label>39</label>
<institution>Department of Genetics and Fundamental Medicine, Bashkir State University</institution>
, Ufa,
<country>Russian Federation</country>
</aff>
<aff id="aff40">
<label>40</label>
<institution>Department of Psychiatry, Dalhousie University</institution>
, Halifax, NS,
<country>Canada</country>
</aff>
<aff id="aff41">
<label>41</label>
<institution>National Institute of Mental Health</institution>
, Klecany,
<country>Czech Republic</country>
</aff>
<aff id="aff42">
<label>42</label>
<institution>Montreal Neurological Institute, McGill University</institution>
, Montreal, QC,
<country>Canada</country>
</aff>
<aff id="aff43">
<label>43</label>
<institution>Department of Human Genetics, McGill University</institution>
, Montreal, QC,
<country>Canada</country>
</aff>
<aff id="aff44">
<label>44</label>
<institution>McGill Group for Suicide Studies and Douglas Research Institute</institution>
, Montreal, QC,
<country>Canada</country>
</aff>
<aff id="aff45">
<label>45</label>
<institution>Department of Psychiatry, McGill University</institution>
, Montreal, QC,
<country>Canada</country>
</aff>
<aff id="aff46">
<label>46</label>
<institution>Département des sciences fondamentales, Université du Québec à Chicoutimi (UQAC)</institution>
, Chicoutimi, QC,
<country>Canada</country>
</aff>
<aff id="aff47">
<label>47</label>
<institution>Department of Psychiatry, Hospital Regional Universitario, Biomedical Institute of Malaga</institution>
, Malaga,
<country>Spain</country>
</aff>
<aff id="aff48">
<label>48</label>
<institution>Center for Research in Environmental Epidemiology</institution>
, Barcelona,
<country>Spain</country>
</aff>
<aff id="aff49">
<label>49</label>
<institution>Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital</institution>
, Bucharest,
<country>Romania</country>
</aff>
</contrib-group>
<author-notes>
<corresp id="caf1">
<label>*</label>
<institution>Institute of Human Genetics, University of Bonn</institution>
, Sigmund-Freud-Strasse 25, Bonn 53127,
<country>Germany</country>
. E-mail:
<email>markus.noethen@uni-bonn.de</email>
</corresp>
<fn fn-type="present-address" id="note1">
<label>50</label>
<p>These authors contributed equally to this work.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub">
<month>11</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="epub">
<day>10</day>
<month>11</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>1</day>
<month>11</month>
<year>2015</year>
</pub-date>
<volume>5</volume>
<issue>11</issue>
<fpage>e678</fpage>
<lpage></lpage>
<history>
<date date-type="received">
<day>20</day>
<month>08</month>
<year>2015</year>
</date>
<date date-type="accepted">
<day>07</day>
<month>09</month>
<year>2015</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright © 2015 Macmillan Publishers Limited</copyright-statement>
<copyright-year>2015</copyright-year>
<copyright-holder>Macmillan Publishers Limited</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>Bipolar disorder (BD) is a severe and highly heritable neuropsychiatric disorder with a lifetime prevalence of 1%. Molecular genetic studies have identified the first BD susceptibility genes. However, the disease pathways remain largely unknown. Accumulating evidence suggests that microRNAs, a class of small noncoding RNAs, contribute to basic mechanisms underlying brain development and plasticity, suggesting their possible involvement in the pathogenesis of several psychiatric disorders, including BD. In the present study, gene-based analyses were performed for all known autosomal microRNAs using the largest genome-wide association data set of BD to date (9747 patients and 14 278 controls). Associated and brain-expressed microRNAs were then investigated in target gene and pathway analyses. Functional analyses of
<italic>miR-499</italic>
and
<italic>miR-708</italic>
were performed in rat hippocampal neurons. Ninety-eight of the six hundred nine investigated microRNAs showed nominally significant
<italic>P</italic>
-values, suggesting that BD-associated microRNAs might be enriched within known microRNA loci. After correction for multiple testing, nine microRNAs showed a significant association with BD. The most promising were
<italic>miR-499</italic>
,
<italic>miR-708</italic>
and
<italic>miR-1908</italic>
. Target gene and pathway analyses revealed 18 significant canonical pathways, including brain development and neuron projection. For
<italic>miR-499</italic>
, four Bonferroni-corrected significant target genes were identified, including the genome-wide risk gene for psychiatric disorder
<italic>CACNB2</italic>
. First results of functional analyses in rat hippocampal neurons neither revealed nor excluded a major contribution of
<italic>miR-499</italic>
or
<italic>miR-708</italic>
to dendritic spine morphogenesis. The present results suggest that research is warranted to elucidate the precise involvement of microRNAs and their downstream pathways in BD.</p>
</abstract>
</article-meta>
</front>
<floats-group>
<fig id="fig1">
<label>Figure 1</label>
<caption>
<p>Quantile–quantile (Q–Q) plot of single-nucleotide polymorphism (SNP)
<italic>P</italic>
-values. The −log10 of the observed genome-wide association studies (GWAS)
<italic>P</italic>
-values for linkage disequilibrium (LD)-pruned SNPs (on the
<italic>y</italic>
axis) are plotted versus the −log 10 of the expected
<italic>P</italic>
-values (under null, on the
<italic>x</italic>
axis). The solid line represents expected uniform distribution. Red dots represent the data distribution of
<italic>P</italic>
-values of SNPs at microRNA loci; blue dots represent SNPs in genes; black dots represent
<italic>P</italic>
-values of intergenic SNPs; and green dots represent the data distribution of all SNPs.</p>
</caption>
<graphic xlink:href="tp2015159f1"></graphic>
</fig>
<fig id="fig2">
<label>Figure 2</label>
<caption>
<p>Regional association plots of
<italic>miR-499</italic>
,
<italic>miR-708</italic>
and
<italic>miR-1908</italic>
. Regional association results for the three most promising associated microRNAs
<italic>miR-499</italic>
(
<bold>a</bold>
),
<italic>miR-708</italic>
(
<bold>b</bold>
) and
<italic>miR-1908</italic>
(
<bold>c</bold>
), and their ±500-kb flanking regions were plotted using LocusZoom (Pruim
<italic>et al.</italic>
<sup>
<xref ref-type="bibr" rid="bib36">36</xref>
</sup>
). The plot of
<italic>miR-1908</italic>
(
<bold>c</bold>
) includes
<italic>miR-611</italic>
, which is also localized at the depicted chromosomal locus.</p>
</caption>
<graphic xlink:href="tp2015159f2"></graphic>
</fig>
<fig id="fig3">
<label>Figure 3</label>
<caption>
<p>Effect of the overexpression of
<italic>miR-499</italic>
and
<italic>miR-708</italic>
on dendritic spine size and density in primary rat hippocampal neurons. DIV14 primary hippocampal neurons were transfected with: (i) empty pmirGLO (250 ng) or (ii) pmirGLO (250 ng) containing
<italic>pri-miR-499</italic>
or
<italic>pri-miR-708</italic>
in the 3'-untranslated repeat of the Firefly luciferase gene and green fluorescent protein (GFP). The transfected neurons were then cultured until DIV19 and fixed for fluorescence microscopy. (
<bold>a</bold>
) Representative images for cells transfected with the indicated pmirGLO constructs or GFP only. A three-dimensional reconstruction was made from seven 45-μm stacks; scale bars, 5 μm. (
<bold>b</bold>
) Spine volume quantification of hippocampal neurons transfected with the indicated pmirGLO constructs. Values are represented as means±s.d. (
<italic>n</italic>
=3; 24 neurons per condition with a 200–250 spine count per cell). (
<bold>c</bold>
) Spine density of hippocampal neurons transfected with the indicated pmirGLO constructs. Values are represented as means±s.d. per 10 μm dendritic length (
<italic>n</italic>
=3; 24 neurons per condition). Data are presented as the mean of three independent transfections normalized to the empty pmirGLO condition±s.d.</p>
</caption>
<graphic xlink:href="tp2015159f3"></graphic>
</fig>
<table-wrap id="tbl1">
<label>Table 1</label>
<caption>
<title>Results of the gene-based tests for the nine microRNAs that withstood Bonferroni correction</title>
</caption>
<table frame="hsides" rules="groups" border="1">
<colgroup>
<col align="left"></col>
<col align="char" char="."></col>
<col align="char" char="."></col>
<col align="center"></col>
<col align="char" char="."></col>
<col align="char" char="."></col>
<col align="center"></col>
<col align="center"></col>
</colgroup>
<thead valign="bottom">
<tr>
<th align="left" valign="top" charoff="50">
<italic>miRNA</italic>
</th>
<th align="center" valign="top" char="." charoff="50">
<italic>Chr</italic>
</th>
<th align="center" valign="top" char="." charoff="50">
<italic>nSNPs</italic>
</th>
<th align="center" valign="top" charoff="50">
<italic>Top SNP</italic>
</th>
<th align="center" valign="top" char="." charoff="50">
<italic>p Top SNP</italic>
</th>
<th align="center" valign="top" char="." charoff="50">
<italic>p Corr Gene</italic>
</th>
<th align="center" valign="top" charoff="50">
<italic>miRNA-assoc. signal</italic>
</th>
<th align="center" valign="top" charoff="50">
<italic>Expr. hum. brain</italic>
</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td align="left" valign="top" charoff="50">
<italic>miR-499</italic>
</td>
<td align="center" valign="top" char="." charoff="50">20</td>
<td align="center" valign="top" char="." charoff="50">27</td>
<td align="left" valign="top" charoff="50">rs3818253</td>
<td align="char" valign="top" char="." charoff="50">6.58 × 10
<sup>−7</sup>
</td>
<td align="char" valign="top" char="." charoff="50">0.0012</td>
<td align="left" valign="top" charoff="50">Yes</td>
<td align="left" valign="top" charoff="50">Yes</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<italic>miR-640</italic>
</td>
<td align="center" valign="top" char="." charoff="50">19</td>
<td align="center" valign="top" char="." charoff="50">21</td>
<td align="left" valign="top" charoff="50">rs2965184</td>
<td align="char" valign="top" char="." charoff="50">7.23 × 10
<sup>−7</sup>
</td>
<td align="char" valign="top" char="." charoff="50">0.0012</td>
<td align="left" valign="top" charoff="50">Yes</td>
<td align="left" valign="top" charoff="50">No</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<italic>miR-708</italic>
</td>
<td align="center" valign="top" char="." charoff="50">11</td>
<td align="center" valign="top" char="." charoff="50">72</td>
<td align="left" valign="top" charoff="50">rs7108878</td>
<td align="char" valign="top" char="." charoff="50">3.45 × 10
<sup>−7</sup>
</td>
<td align="char" valign="top" char="." charoff="50">0.0012</td>
<td align="left" valign="top" charoff="50">Yes</td>
<td align="left" valign="top" charoff="50">Yes</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<italic>miR-581</italic>
</td>
<td align="center" valign="top" char="." charoff="50">5</td>
<td align="center" valign="top" char="." charoff="50">36</td>
<td align="left" valign="top" charoff="50">rs697112</td>
<td align="char" valign="top" char="." charoff="50">3.61 × 10
<sup>−6</sup>
</td>
<td align="char" valign="top" char="." charoff="50">0.0073</td>
<td align="left" valign="top" charoff="50">Yes</td>
<td align="left" valign="top" charoff="50">No</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<italic>miR-644</italic>
</td>
<td align="center" valign="top" char="." charoff="50">20</td>
<td align="center" valign="top" char="." charoff="50">12</td>
<td align="left" valign="top" charoff="50">rs7269526</td>
<td align="char" valign="top" char="." charoff="50">1.22 × 10
<sup>−5</sup>
</td>
<td align="char" valign="top" char="." charoff="50">0.0104</td>
<td align="left" valign="top" charoff="50">No</td>
<td align="left" valign="top" charoff="50">No</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<italic>miR-135a-1</italic>
</td>
<td align="center" valign="top" char="." charoff="50">3</td>
<td align="center" valign="top" char="." charoff="50">20</td>
<td align="left" valign="top" charoff="50">rs9311474</td>
<td align="char" valign="top" char="." charoff="50">2.16 × 10
<sup>−5</sup>
</td>
<td align="char" valign="top" char="." charoff="50">0.0122</td>
<td align="left" valign="top" charoff="50">No</td>
<td align="left" valign="top" charoff="50">Yes</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<italic>let-7 g</italic>
</td>
<td align="center" valign="top" char="." charoff="50">3</td>
<td align="center" valign="top" char="." charoff="50">9</td>
<td align="left" valign="top" charoff="50">rs6445358</td>
<td align="char" valign="top" char="." charoff="50">2.23 × 10
<sup>−5</sup>
</td>
<td align="char" valign="top" char="." charoff="50">0.0305</td>
<td align="left" valign="top" charoff="50">No</td>
<td align="left" valign="top" charoff="50">Yes</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<italic>miR-1908</italic>
</td>
<td align="center" valign="top" char="." charoff="50">11</td>
<td align="center" valign="top" char="." charoff="50">16</td>
<td align="left" valign="top" charoff="50">rs174575</td>
<td align="char" valign="top" char="." charoff="50">2.85 × 10
<sup>−5</sup>
</td>
<td align="char" valign="top" char="." charoff="50">0.0353</td>
<td align="left" valign="top" charoff="50">Yes</td>
<td align="left" valign="top" charoff="50">Yes</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<italic>miR-611</italic>
</td>
<td align="center" valign="top" char="." charoff="50">11</td>
<td align="center" valign="top" char="." charoff="50">23</td>
<td align="left" valign="top" charoff="50">rs174535</td>
<td align="char" valign="top" char="." charoff="50">5.03 × 10
<sup>−5</sup>
</td>
<td align="char" valign="top" char="." charoff="50">0.0457</td>
<td align="left" valign="top" charoff="50">No</td>
<td align="left" valign="top" charoff="50">No</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="t1-fn1">
<p>Abbreviations: Chr, chromosome; expr. hum. brain, expression in the human brain according to Ziats and Rennert;
<sup>
<xref ref-type="bibr" rid="bib37">37</xref>
</sup>
miRNA, microRNA; miRNA-assoc. signal, specificity of the associated finding in the regional association plot; p Corr Gene, Bonferroni-corrected gene-based
<italic>P</italic>
-value; p Top SNP,
<italic>P</italic>
-value of the Top SNP within gene; nSNPs, number of investigated SNPs; SNP, single-nucleotide polymorphism.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="tbl2">
<label>Table 2</label>
<caption>
<title>Target gene and pathway analysis for
<italic>miR-499</italic>
,
<italic>miR-708</italic>
and
<italic>miR-1908</italic>
</title>
</caption>
<table frame="hsides" rules="groups" border="1">
<colgroup>
<col align="left"></col>
<col align="char" char="."></col>
<col align="char" char="."></col>
<col align="center"></col>
<col align="char" char="."></col>
<col align="char" char="."></col>
</colgroup>
<thead valign="bottom">
<tr>
<th align="left" valign="top" charoff="50">
<italic>MicroRNA</italic>
</th>
<th align="center" valign="top" char="." charoff="50">
<italic>No. of brain-expressed target genes</italic>
</th>
<th align="center" valign="top" char="." charoff="50">
<italic>No. of brain-expressed target genes</italic>
, P
<italic><0.05</italic>
</th>
<th align="char" valign="top" char="." charoff="50">
<italic>P enrichment</italic>
</th>
<th align="center" valign="top" char="." charoff="50">
<italic>No. of significant targets (corr)</italic>
</th>
<th align="center" valign="top" char="." charoff="50">
<italic>No. of significant pathways</italic>
</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td align="left" valign="top" charoff="50">
<italic>miR-499-5p</italic>
</td>
<td align="center" valign="top" char="." charoff="50">286</td>
<td align="center" valign="top" char="." charoff="50">59</td>
<td align="center" valign="top" charoff="50">0.7172</td>
<td align="center" valign="top" char="." charoff="50">4</td>
<td align="center" valign="top" char="." charoff="50">12</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<italic>miR-708-5p</italic>
</td>
<td align="center" valign="top" char="." charoff="50">174</td>
<td align="center" valign="top" char="." charoff="50">37</td>
<td align="center" valign="top" charoff="50">0.9265</td>
<td align="center" valign="top" char="." charoff="50">2</td>
<td align="center" valign="top" char="." charoff="50">1</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<italic>miR-1908-5p</italic>
</td>
<td align="center" valign="top" char="." charoff="50">56</td>
<td align="center" valign="top" char="." charoff="50">17</td>
<td align="center" valign="top" charoff="50">0.1422</td>
<td align="center" valign="top" char="." charoff="50">1</td>
<td align="center" valign="top" char="." charoff="50">5</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="t2-fn1">
<p>Abbreviations: No. of significant pathways, number of significant pathways at
<italic>P</italic>
≤0.05; No. of significant targets (corr), number of significant target genes after Bonferroni correction for multiple testing; P enrichment
<italic>, P</italic>
-value of the enrichment analysis (
<italic>X</italic>
<sup>2</sup>
-test).</p>
</fn>
<fn id="t2-fn2">
<p>Results of the target gene analysis for the three brain-expressed microRNAs
<italic>miR-499</italic>
,
<italic>miR-708</italic>
and
<italic>miR-1908</italic>
that were associated with bipolar disorder after correction for multiple testing.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</floats-group>
</pmc>
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