Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
28166306
TITLE
Identification of shared risk loci and pathways for bipolar disorder and schizophrenia.
ABSTRACT
NlmCategory: UNASSIGNED
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.
DATE PUBLISHED
2017
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2016/10/10
accepted 2017/01/23
entrez 2017/02/07 06:00
pubmed 2017/02/07 06:00
medline 2017/02/07 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Forstner AJ Forstner Andreas J AJ Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
Hecker J Hecker Julian J Institute for Genomics Mathematics, University of Bonn, Bonn, Germany.
Hofmann A Hofmann Andrea A Institute of Medical Microbiology, Immunology and Parasitology, University of Bonn, Bonn, Germany.
Maaser A Maaser Anna A Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
Reinbold CS Reinbold Céline S CS Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
Mühleisen TW Mühleisen Thomas W TW Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Juelich, Germany.
Leber M Leber Markus M Department of Psychiatry & Psychotherapy, University of Cologne, Cologne, Germany.
Strohmaier J Strohmaier Jana J Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg, Mannheim, Germany.
Degenhardt F Degenhardt Franziska F Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
Treutlein J Treutlein Jens J Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg, Mannheim, Germany.
Mattheisen M Mattheisen Manuel M The Lundbeck Foundation Initiative for integrative Psychiatric Research, iPSYCH, Aarhus and Copenhagen, Denmark.
Schumacher J Schumacher Johannes J Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
Streit F Streit Fabian F Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg, Mannheim, Germany.
Meier S Meier Sandra S National Centre Register-Based Research, Aarhus University, Aarhus, Denmark.
Herms S Herms Stefan S Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
Hoffmann P Hoffmann Per P Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
Lacour A Lacour André A German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Witt SH Witt Stephanie H SH Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg, Mannheim, Germany.
Reif A Reif Andreas A Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt am Main, Frankfurt am Main, Germany.
Müller-Myhsok B Müller-Myhsok Bertram B University of Liverpool, Institute of Translational Medicine, Liverpool, United Kingdom.
Lucae S Lucae Susanne S Max Planck Institute of Psychiatry, Munich, Germany.
Maier W Maier Wolfgang W Department of Psychiatry, University of Bonn, Bonn, Germany.
Schwarz M Schwarz Markus M Psychiatric Center Nordbaden, Wiesloch, Germany.
Vedder H Vedder Helmut H Psychiatric Center Nordbaden, Wiesloch, Germany.
Kammerer-Ciernioch J Kammerer-Ciernioch Jutta J Center of Psychiatry Weinsberg, Weinsberg, Germany.
Pfennig A Pfennig Andrea A Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany.
Bauer M Bauer Michael M Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany.
Hautzinger M Hautzinger Martin M Department of Psychology, Clinical Psychology and Psychotherapy, Eberhard Karls University Tübingen, Tübingen, Germany.
Moebus S Moebus Susanne S Institute of Medical Informatics, Biometry and Epidemiology, University Duisburg-Essen, Essen, Germany.
Schenk LM Schenk Lorena M LM Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
Fischer SB Fischer Sascha B SB Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
Sivalingam S Sivalingam Sugirthan S Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
Czerski PM Czerski Piotr M PM Laboratory of Psychiatric Genetics, Department of Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
Hauser J Hauser Joanna J Laboratory of Psychiatric Genetics, Department of Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
Lissowska J Lissowska Jolanta J Department of Cancer Epidemiology and Prevention, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology Warsaw, Warsaw, Poland.
Szeszenia-Dabrowska N Szeszenia-Dabrowska Neonila N Department of Epidemiology, Nofer Institute of Occupational Medicine, Lodz, Poland.
Brennan P Brennan Paul P Genetic Epidemiology Group, International Agency for Research on Cancer (IARC), Lyon, France.
McKay JD McKay James D JD Genetic Cancer Susceptibility Group, International Agency for Research on Cancer (IARC), Lyon, France.
Wright A Wright Adam A Black Dog Institute, Prince of Wales Hospital, Randwick, Australia.
Mitchell PB Mitchell Philip B PB Black Dog Institute, Prince of Wales Hospital, Randwick, Australia.
Fullerton JM Fullerton Janice M JM School of Medical Sciences Faculty of Medicine, University of New South Wales, Sydney, Australia.
Schofield PR Schofield Peter R PR School of Medical Sciences Faculty of Medicine, University of New South Wales, Sydney, Australia.
Montgomery GW Montgomery Grant W GW Queensland Institute of Medical Research (QIMR), Brisbane, Australia.
Medland SE Medland Sarah E SE Queensland Institute of Medical Research (QIMR), Brisbane, Australia.
Gordon SD Gordon Scott D SD Queensland Institute of Medical Research (QIMR), Brisbane, Australia.
Martin NG Martin Nicholas G NG Queensland Institute of Medical Research (QIMR), Brisbane, Australia.
Krasnov V Krasnov Valery V Moscow Research Institute of Psychiatry, Moscow, Russian Federation.
Chuchalin A Chuchalin Alexander A Institute of Pulmonology, Russian State Medical University, Moscow, Russian Federation.
Babadjanova G Babadjanova Gulja G Institute of Pulmonology, Russian State Medical University, Moscow, Russian Federation.
Pantelejeva G Pantelejeva Galina G Russian Academy of Medical Sciences, Mental Health Research Center, Moscow, Russian Federation.
Abramova LI Abramova Lilia I LI Russian Academy of Medical Sciences, Mental Health Research Center, Moscow, Russian Federation.
Tiganov AS Tiganov Alexander S AS Russian Academy of Medical Sciences, Mental Health Research Center, Moscow, Russian Federation.
Polonikov A Polonikov Alexey A Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, Kursk, Russian Federation.
Khusnutdinova E Khusnutdinova Elza E Department of Genetics and Fundamental Medicine of Bashkir State University, Ufa, Russian Federation.
Alda M Alda Martin M National Institute of Mental Health, Klecany, Czech Republic.
Cruceanu C Cruceanu Cristiana C McGill Group for Suicide Studies & Douglas Research Institute, Montreal, Canada.
Rouleau GA Rouleau Guy A GA Montreal Neurological Institute, McGill University, Montreal, Canada.
Turecki G Turecki Gustavo G Department of Psychiatry, McGill University, Montreal, Canada.
Laprise C Laprise Catherine C Département des sciences fondamentales, Université du Québec à Chicoutimi (UQAC), Saguenay, Canada.
Rivas F Rivas Fabio F Department of Psychiatry, Hospital Regional Universitario, Biomedical Institute of Malaga, Malaga, Spain.
Mayoral F Mayoral Fermin F Department of Psychiatry, Hospital Regional Universitario, Biomedical Institute of Malaga, Malaga, Spain.
Kogevinas M Kogevinas Manolis M Center for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
Grigoroiu-Serbanescu M Grigoroiu-Serbanescu Maria M Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest, Romania.
Becker T Becker Tim T Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany.
Schulze TG Schulze Thomas G TG Institute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University Munich, Munich, Germany.
Rietschel M Rietschel Marcella M Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg, Mannheim, Germany.
Cichon S Cichon Sven S Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Juelich, Germany.
Fier H Fier Heide H Institute for Genomics Mathematics, University of Bonn, Bonn, Germany.
Nöthen MM Nöthen Markus M MM Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
INVESTIGATORS
JOURNAL
VOLUME: 12
ISSUE: 2
TITLE: PloS one
ISOABBREVIATION: PLoS ONE
YEAR: 2017
MONTH:
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1932-6203
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: PLoS One
COUNTRY: United States
ISSNLINKING: 1932-6203
NLMUNIQUEID: 101285081
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
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