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PMID |
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TITLE |
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Identification of shared risk loci and pathways for bipolar disorder and schizophrenia. |
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ABSTRACT |
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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. |
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DATE PUBLISHED |
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HISTORY |
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PUBSTATUS |
PUBSTATUSDATE |
received |
2016/10/10 |
accepted |
2017/01/23 |
entrez |
2017/02/07 06:00 |
pubmed |
2017/02/07 06:00 |
medline |
2017/08/26 06:00 |
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AUTHORS |
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NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
Forstner AJ |
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Forstner |
Andreas J |
AJ |
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Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland. |
Hecker J |
|
Hecker |
Julian |
J |
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Institute for Genomics Mathematics, University of Bonn, Bonn, Germany. |
Hofmann A |
|
Hofmann |
Andrea |
A |
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Institute of Medical Microbiology, Immunology and Parasitology, University of Bonn, Bonn, Germany. |
Maaser A |
|
Maaser |
Anna |
A |
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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 |
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Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Juelich, Germany. |
Leber M |
|
Leber |
Markus |
M |
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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 |
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Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany. |
Treutlein J |
|
Treutlein |
Jens |
J |
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Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg, Mannheim, Germany. |
Mattheisen M |
|
Mattheisen |
Manuel |
M |
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The Lundbeck Foundation Initiative for integrative Psychiatric Research, iPSYCH, Aarhus and Copenhagen, Denmark. |
Schumacher J |
|
Schumacher |
Johannes |
J |
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Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany. |
Streit F |
|
Streit |
Fabian |
F |
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Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg, Mannheim, Germany. |
Meier S |
|
Meier |
Sandra |
S |
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National Centre Register-Based Research, Aarhus University, Aarhus, Denmark. |
Herms S |
|
Herms |
Stefan |
S |
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Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland. |
Hoffmann P |
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Hoffmann |
Per |
P |
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Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland. |
Lacour A |
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Lacour |
André |
A |
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German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany. |
Witt SH |
|
Witt |
Stephanie H |
SH |
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Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg, Mannheim, Germany. |
Reif A |
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Reif |
Andreas |
A |
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Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt am Main, Frankfurt am Main, Germany. |
Müller-Myhsok B |
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Müller-Myhsok |
Bertram |
B |
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University of Liverpool, Institute of Translational Medicine, Liverpool, United Kingdom. |
Lucae S |
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Lucae |
Susanne |
S |
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Max Planck Institute of Psychiatry, Munich, Germany. |
Maier W |
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Maier |
Wolfgang |
W |
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Department of Psychiatry, University of Bonn, Bonn, Germany. |
Schwarz M |
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Schwarz |
Markus |
M |
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Psychiatric Center Nordbaden, Wiesloch, Germany. |
Vedder H |
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Vedder |
Helmut |
H |
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Psychiatric Center Nordbaden, Wiesloch, Germany. |
Kammerer-Ciernioch J |
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Kammerer-Ciernioch |
Jutta |
J |
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Center of Psychiatry Weinsberg, Weinsberg, Germany. |
Pfennig A |
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Pfennig |
Andrea |
A |
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Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany. |
Bauer M |
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Bauer |
Michael |
M |
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Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany. |
Hautzinger M |
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Hautzinger |
Martin |
M |
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Department of Psychology, Clinical Psychology and Psychotherapy, Eberhard Karls University Tübingen, Tübingen, Germany. |
Moebus S |
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Moebus |
Susanne |
S |
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Institute of Medical Informatics, Biometry and Epidemiology, University Duisburg-Essen, Essen, Germany. |
Schenk LM |
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Schenk |
Lorena M |
LM |
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Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany. |
Fischer SB |
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Fischer |
Sascha B |
SB |
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Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland. |
Sivalingam S |
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Sivalingam |
Sugirthan |
S |
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Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany. |
Czerski PM |
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Czerski |
Piotr M |
PM |
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Laboratory of Psychiatric Genetics, Department of Psychiatry, Poznan University of Medical Sciences, Poznan, Poland. |
Hauser J |
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Hauser |
Joanna |
J |
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Laboratory of Psychiatric Genetics, Department of Psychiatry, Poznan University of Medical Sciences, Poznan, Poland. |
Lissowska J |
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Lissowska |
Jolanta |
J |
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Department of Cancer Epidemiology and Prevention, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology Warsaw, Warsaw, Poland. |
Szeszenia-Dabrowska N |
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Szeszenia-Dabrowska |
Neonila |
N |
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Department of Epidemiology, Nofer Institute of Occupational Medicine, Lodz, Poland. |
Brennan P |
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Brennan |
Paul |
P |
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Genetic Epidemiology Group, International Agency for Research on Cancer (IARC), Lyon, France. |
McKay JD |
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McKay |
James D |
JD |
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Genetic Cancer Susceptibility Group, International Agency for Research on Cancer (IARC), Lyon, France. |
Wright A |
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Wright |
Adam |
A |
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Black Dog Institute, Prince of Wales Hospital, Randwick, Australia. |
Mitchell PB |
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Mitchell |
Philip B |
PB |
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Black Dog Institute, Prince of Wales Hospital, Randwick, Australia. |
Fullerton JM |
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Fullerton |
Janice M |
JM |
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School of Medical Sciences Faculty of Medicine, University of New South Wales, Sydney, Australia. |
Schofield PR |
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Schofield |
Peter R |
PR |
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School of Medical Sciences Faculty of Medicine, University of New South Wales, Sydney, Australia. |
Montgomery GW |
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Montgomery |
Grant W |
GW |
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Queensland Institute of Medical Research (QIMR), Brisbane, Australia. |
Medland SE |
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Medland |
Sarah E |
SE |
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Queensland Institute of Medical Research (QIMR), Brisbane, Australia. |
Gordon SD |
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Gordon |
Scott D |
SD |
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Queensland Institute of Medical Research (QIMR), Brisbane, Australia. |
Martin NG |
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Martin |
Nicholas G |
NG |
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Queensland Institute of Medical Research (QIMR), Brisbane, Australia. |
Krasnov V |
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Krasnov |
Valery |
V |
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Moscow Research Institute of Psychiatry, Moscow, Russian Federation. |
Chuchalin A |
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Chuchalin |
Alexander |
A |
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Institute of Pulmonology, Russian State Medical University, Moscow, Russian Federation. |
Babadjanova G |
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Babadjanova |
Gulja |
G |
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Institute of Pulmonology, Russian State Medical University, Moscow, Russian Federation. |
Pantelejeva G |
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Pantelejeva |
Galina |
G |
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Russian Academy of Medical Sciences, Mental Health Research Center, Moscow, Russian Federation. |
Abramova LI |
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Abramova |
Lilia I |
LI |
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Russian Academy of Medical Sciences, Mental Health Research Center, Moscow, Russian Federation. |
Tiganov AS |
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Tiganov |
Alexander S |
AS |
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Russian Academy of Medical Sciences, Mental Health Research Center, Moscow, Russian Federation. |
Polonikov A |
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Polonikov |
Alexey |
A |
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Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, Kursk, Russian Federation. |
Khusnutdinova E |
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Khusnutdinova |
Elza |
E |
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Department of Genetics and Fundamental Medicine of Bashkir State University, Ufa, Russian Federation. |
Alda M |
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Alda |
Martin |
M |
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National Institute of Mental Health, Klecany, Czech Republic. |
Cruceanu C |
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Cruceanu |
Cristiana |
C |
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McGill Group for Suicide Studies & Douglas Research Institute, Montreal, Canada. |
Rouleau GA |
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Rouleau |
Guy A |
GA |
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Montreal Neurological Institute, McGill University, Montreal, Canada. |
Turecki G |
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Turecki |
Gustavo |
G |
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Department of Psychiatry, McGill University, Montreal, Canada. |
Laprise C |
|
Laprise |
Catherine |
C |
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Département des sciences fondamentales, Université du Québec à Chicoutimi (UQAC), Saguenay, Canada. |
Rivas F |
|
Rivas |
Fabio |
F |
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Department of Psychiatry, Hospital Regional Universitario, Biomedical Institute of Malaga, Malaga, Spain. |
Mayoral F |
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Mayoral |
Fermin |
F |
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Department of Psychiatry, Hospital Regional Universitario, Biomedical Institute of Malaga, Malaga, Spain. |
Kogevinas M |
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Kogevinas |
Manolis |
M |
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Center for Research in Environmental Epidemiology (CREAL), Barcelona, Spain. |
Grigoroiu-Serbanescu M |
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Grigoroiu-Serbanescu |
Maria |
M |
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Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest, Romania. |
Becker T |
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Becker |
Tim |
T |
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Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany. |
Schulze TG |
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Schulze |
Thomas G |
TG |
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Institute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University Munich, Munich, Germany. |
Rietschel M |
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Rietschel |
Marcella |
M |
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Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg, Mannheim, Germany. |
Cichon S |
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Cichon |
Sven |
S |
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Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Juelich, Germany. |
Fier H |
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Fier |
Heide |
H |
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Institute for Genomics Mathematics, University of Bonn, Bonn, Germany. |
Nöthen MM |
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Nöthen |
Markus M |
MM |
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Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany. |
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INVESTIGATORS |
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JOURNAL |
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VOLUME: 12 |
ISSUE: 2 |
TITLE: PloS one |
ISOABBREVIATION: PLoS One |
YEAR: 2017 |
MONTH: |
DAY: |
MEDLINEDATE: |
SEASON: |
CITEDMEDIUM: Internet |
ISSN: 1932-6203 |
ISSNTYPE: Electronic |
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MEDLINE JOURNAL |
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MEDLINETA: PLoS One |
COUNTRY: United States |
ISSNLINKING: 1932-6203 |
NLMUNIQUEID: 101285081 |
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PUBLICATION TYPE |
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PUBLICATIONTYPE TEXT |
Journal Article |
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COMMENTS AND CORRECTIONS |
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GRANTS |
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GENERAL NOTE |
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KEYWORDS |
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MESH HEADINGS |
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DESCRIPTORNAME |
QUALIFIERNAME |
Bipolar Disorder |
metabolism |
Genetic Linkage |
metabolism |
Genetic Predisposition to Disease |
metabolism |
Genome-Wide Association Study |
metabolism |
Humans |
metabolism |
Linkage Disequilibrium |
metabolism |
Polymorphism, Single Nucleotide |
metabolism |
Quantitative Trait Loci |
metabolism |
Risk |
metabolism |
Schizophrenia |
metabolism |
Signal Transduction |
metabolism |
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SUPPLEMENTARY MESH |
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GENE SYMBOLS |
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CHEMICALS |
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OTHER ID's |
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