Identification of shared risk loci and pathways for bipolar disorder and schizophrenia

Publikation: Forskning - peer reviewTidsskriftartikel

DOI

  • Andreas J Forstner
    Andreas J ForstnerInstitute of Human Genetics, University of Bonn, Bonn, Germany.Tyskland
  • Julian Hecker
    Julian HeckerInstitute for Genomics Mathematics, University of Bonn, Bonn, Germany.
  • Andrea Hofmann
    Andrea HofmannInstitute of Human Genetics, University of Bonn, Bonn, Germany.
  • Anna Maaser
    Anna MaaserInstitute of Human Genetics, University of Bonn, Bonn, Germany.
  • Céline S Reinbold
    Céline S Reinbold1] Institute of Human Genetics, University of Bonn, Bonn, Germany. [2] Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany. [3] Division of Medical Genetics, University Hospital, Basel, Switzerland. [4] Human Genetics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland.
  • Thomas W Mühleisen
    Thomas W Mühleisen
  • Markus Leber
    Markus LeberDepartment of Psychiatry & Psychotherapy, University of Cologne, Cologne, Germany.
  • Jana Strohmaier
    Jana StrohmaierDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg, Mannheim, Germany.
  • Franziska Degenhardt
    Franziska DegenhardtInstitute of Human Genetics, University of Bonn, Bonn, Germany.
  • Jens Treutlein
    Jens TreutleinDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg, Mannheim, Germany.
  • Manuel Mattheisen
  • Johannes Schumacher
    Johannes SchumacherInstitute of Human Genetics, University of Bonn, Bonn, Germany.
  • Fabian Streit
    Fabian StreitDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg, Mannheim, Germany.
  • Sandra Meier
    Sandra Meier
  • Stefan Herms
    Stefan HermsInstitute of Human Genetics, University of Bonn, Bonn, Germany.
  • Per Hoffmann
    Per HoffmannInstitute of Human Genetics, University of Bonn, Bonn, Germany.
  • André Lacour
    André LacourGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
  • Stephanie H Witt
    Stephanie H WittDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg, Mannheim, Germany.
  • Andreas Reif
    Andreas ReifDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt am Main, Frankfurt am Main, Germany.
  • Bertram Müller-Myhsok
    Bertram Müller-MyhsokMax Planck Institute of Psychiatry, Munich, Germany.
  • Susanne Lucae
    Susanne LucaeMax Planck Institute of Psychiatry, Munich, Germany.
  • Wolfgang Maier
    Wolfgang MaierDepartment of Psychiatry, University of Bonn, Bonn, Germany.
  • Markus Schwarz
    Markus SchwarzPsychiatric Center Nordbaden, Wiesloch, Germany.
  • Helmut Vedder
    Helmut VedderPsychiatric Center Nordbaden, Wiesloch, Germany.
  • Jutta Kammerer-Ciernioch
    Jutta Kammerer-CierniochCenter of Psychiatry Weinsberg, Weinsberg, Germany.
  • Andrea Pfennig
    Andrea PfennigDepartment of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany.
  • Michael Bauer
    Michael BauerDepartment of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany.
  • Martin Hautzinger
    Martin HautzingerDepartment of Psychology, Clinical Psychology and Psychotherapy, Eberhard Karls University Tübingen, Tübingen, Germany.
  • Susanne Moebus
    Susanne MoebusInstitute of Medical Informatics, Biometry and Epidemiology, University Duisburg-Essen, Essen, Germany.
  • Lorena M Schenk
    Lorena M SchenkInstitute of Human Genetics, University of Bonn, Bonn, Germany.
  • Sascha B Fischer
    Sascha B FischerHuman Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland.
  • Sugirthan Sivalingam
    Sugirthan SivalingamInstitute of Human Genetics, University of Bonn, Bonn, Germany.
  • Piotr M Czerski
    Piotr M CzerskiLaboratory of Psychiatric Genetics, Department of Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
  • Joanna Hauser
    Joanna HauserLaboratory of Psychiatric Genetics, Department of Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
  • Jolanta Lissowska
    Jolanta LissowskaDepartment of Cancer Epidemiology and Prevention, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology Warsaw, Warsaw, Poland.
  • Neonila Szeszenia-Dabrowska
    Neonila Szeszenia-DabrowskaDepartment of Epidemiology, Nofer Institute of Occupational Medicine, Lodz, Poland.
  • Paul Brennan
    Paul BrennanGenetic Epidemiology Group, International Agency for Research on Cancer (IARC), Lyon, France.
  • James D McKay
    James D McKayGenetic Cancer Susceptibility Group, International Agency for Research on Cancer (IARC), Lyon, France.
  • Adam Wright
    Adam WrightSchool of Psychiatry, University of New South Wales, Randwick, Australia.
  • Philip B Mitchell
    Philip B MitchellSchool of Psychiatry, University of New South Wales, Randwick, Australia.
  • Janice M Fullerton
    Janice M FullertonNeuroscience Research Australia, Sydney, Australia.
  • Peter R Schofield
    Peter R SchofieldNeuroscience Research Australia, Sydney, Australia.
  • Grant W Montgomery
    Grant W MontgomeryQueensland Institute of Medical Research (QIMR), Brisbane, Australia.
  • Sarah E Medland
    Sarah E MedlandQueensland Institute of Medical Research (QIMR), Brisbane, Australia.
  • Scott D Gordon
    Scott D GordonQueensland Institute of Medical Research (QIMR), Brisbane, Australia.
  • Nicholas G Martin
    Nicholas G MartinQueensland Institute of Medical Research (QIMR), Brisbane, Australia.
  • Valery Krasnov
    Valery KrasnovMoscow Research Institute of Psychiatry, Moscow 107258, Russian Federation.
  • Alexander Chuchalin
    Alexander ChuchalinInstitute of Pulmonology, Russian State Medical University, Moscow, Russian Federation.
  • Gulja Babadjanova
    Gulja BabadjanovaInstitute of Pulmonology, Russian State Medical University, Moscow, Russian Federation.
  • Galina Pantelejeva
    Galina PantelejevaRussian Academy of Medical Sciences, Mental Health Research Center, Moscow, Russian Federation.
  • Lilia I Abramova
    Lilia I AbramovaRussian Academy of Medical Sciences, Mental Health Research Center, Moscow, Russian Federation.
  • Alexander S Tiganov
    Alexander S TiganovRussian Academy of Medical Sciences, Mental Health Research Center, Moscow, Russian Federation.
  • Alexey Polonikov
    Alexey PolonikovDepartment of Biology, Medical Genetics and Ecology, Kursk State Medical University, Kursk, Russian Federation.
  • Elza Khusnutdinova
    Elza KhusnutdinovaInstitute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Sciences, Ufa, Russian Federation.
  • Martin Alda
    Martin AldaDepartment of Psychiatry, Dalhousie University, Halifax, Canada.
  • Cristiana Cruceanu
    Cristiana CruceanuMontreal Neurological Institute, McGill University, Montreal, Canada.
  • Guy A Rouleau
    Guy A RouleauMontreal Neurological Institute, McGill University, Montreal, Canada.
  • Gustavo Turecki
    Gustavo TureckiDepartment of Human Genetics, McGill University, Montreal, Canada.
  • Catherine Laprise
    Catherine LapriseDépartement des sciences fondamentales, Université du Québec à Chicoutimi (UQAC), Saguenay, Canada.
  • Fabio Rivas
    Fabio RivasDepartment of Psychiatry, Hospital Regional Universitario, Biomedical Institute of Malaga, Malaga, Spain.
  • Fermin Mayoral
    Fermin MayoralDepartment of Psychiatry, Hospital Regional Universitario, Biomedical Institute of Malaga, Malaga, Spain.
  • Manolis Kogevinas
    Manolis KogevinasCenter for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
  • Maria Grigoroiu-Serbanescu
    Maria Grigoroiu-SerbanescuBiometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest, Romania.
  • Tim Becker
    Tim BeckerGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
  • Thomas G Schulze
    Thomas G SchulzeInstitute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University Munich, Munich, Germany.
  • Marcella Rietschel
    Marcella RietschelDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg, Mannheim, Germany.
  • Sven Cichon
    Sven CichonInstitute of Human Genetics, University of Bonn, Bonn, Germany.
  • Heide Fier
    Heide FierInstitute for Genomics Mathematics, University of Bonn, Bonn, Germany.
  • Markus M Nöthen
    Markus M NöthenInstitute of Human Genetics, University of Bonn, Bonn, Germany.

Bipolar disorder (BD) is a highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. BD shows substantial clinical and genetic overlap with other psychiatric disorders, in particular schizophrenia (SCZ). The genes underlying this etiological overlap remain largely unknown. A recent SCZ genome wide association study (GWAS) by the Psychiatric Genomics Consortium identified 128 independent genome-wide significant single nucleotide polymorphisms (SNPs). The present study investigated whether these SCZ-associated SNPs also contribute to BD development through the performance of association testing in a large BD GWAS dataset (9747 patients, 14278 controls). After re-imputation and correction for sample overlap, 22 of 107 investigated SCZ SNPs showed nominal association with BD. The number of shared SCZ-BD SNPs was significantly higher than expected (p = 1.46x10-8). This provides further evidence that SCZ-associated loci contribute to the development of BD. Two SNPs remained significant after Bonferroni correction. The most strongly associated SNP was located near TRANK1, which is a reported genome-wide significant risk gene for BD. Pathway analyses for all shared SCZ-BD SNPs revealed 25 nominally enriched gene-sets, which showed partial overlap in terms of the underlying genes. The enriched gene-sets included calcium- and glutamate signaling, neuropathic pain signaling in dorsal horn neurons, and calmodulin binding. The present data provide further insights into shared risk loci and disease-associated pathways for BD and SCZ. This may suggest new research directions for the treatment and prevention of these two major psychiatric disorders.

OriginalsprogEngelsk
TidsskriftPLoS ONE
Vol/bind12
Tidsskriftsnummer2
Sider (fra-til)e0171595
ISSN1932-6203
DOI
StatusUdgivet - 2017

Se relationer på Aarhus Universitet Citationsformater

ID: 108936260