Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder
Background: Bipolar disorder (BD) is a common and highly heritable disorder of mood. Genome-wide association studies (GWAS) have identified several independent susceptibility loci. In order to extract more biological information from GWAS data, multi-locus approaches represent powerful tools since t...
Ausführliche Beschreibung
Autor*in: |
Mühleisen, Thomas W. - 1975- [verfasserIn] Streit, Fabian - 1982- [verfasserIn] Strohmaier, Jana - 1980- [verfasserIn] Treutlein, Jens - 1968- [verfasserIn] Witt, Stephanie - 1970- [verfasserIn] Rietschel, Marcella - 1957- [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2018 |
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Schlagwörter: |
GRB2 events in ERBB2 signaling |
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Anmerkung: |
Available online: 14 November 2017 Gesehen am 22.08.2018 |
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Umfang: |
6 |
Übergeordnetes Werk: |
Enthalten in: Journal of affective disorders - Amsterdam [u.a.] : Elsevier Science, 1979, 228(2018), Seite 20-25 |
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Übergeordnetes Werk: |
volume:228 ; year:2018 ; pages:20-25 ; extent:6 |
Links: |
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DOI / URN: |
10.1016/j.jad.2017.11.068 |
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Katalog-ID: |
1580279392 |
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245 | 1 | 0 | |a Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder |c Thomas W. Mühleisen, Céline S. Reinbold, Andreas J. Forstner, Lilia I. Abramova, Martin Alda, Gulja Babadjanova, Michael Bauer, Paul Brennan, Alexander Chuchalin, Cristiana Cruceanu, Piotr M. Czerski, Franziska Degenhardt, Sascha B. Fischer, Janice M. Fullerton, Scott D. Gordon, Maria Grigoroiu-Serbanescu, Paul Grof, Joanna Hauser, Martin Hautzinger, Stefan Herms, Per Hoffmann, Jutta Kammerer-Ciernioch, Elza Khusnutdinova, Manolis Kogevinas, Valery Krasnov, André Lacour, Catherine Laprise, Markus Leber, Jolanta Lissowska, Susanne Lucae, Anna Maaser, Wolfgang Maier, Nicholas G. Martin, Manuel Mattheisen, Fermin Mayoral, James D. McKay, Sarah E. Medland, Philip B. Mitchell, Susanne Moebus, Grant W. Montgomery, Bertram Müller-Myhsok, Lilijana Oruc, Galina Pantelejeva, Andrea Pfennig, Lejla Pojskic, Alexey Polonikov, Andreas Reif, Fabio Rivas, Guy A. Rouleau, Lorena M. Schenk, Peter R. Schofield, Markus Schwarz, Fabian Streit, Jana Strohmaier, Neonila Szeszenia-Dabrowska, Alexander S. Tiganov, Jens Treutlein, Gustavo Turecki, Helmut Vedder, Stephanie H. Witt, Thomas G. Schulze, Marcella Rietschel, Markus M. Nöthen, Sven Cichon |
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520 | |a Background: Bipolar disorder (BD) is a common and highly heritable disorder of mood. Genome-wide association studies (GWAS) have identified several independent susceptibility loci. In order to extract more biological information from GWAS data, multi-locus approaches represent powerful tools since they utilize knowledge about biological processes to integrate functional sets of genes at strongly to moderately associated loci. Methods: We conducted gene set enrichment analyses (GSEA) using 2.3 million single-nucleotide polymorphisms, 397 Reactome pathways and 24,025 patients with BD and controls. RNA expression of implicated individual genes and gene sets were examined in post-mortem brains across lifespan. Results: Two pathways showed a significant enrichment after correction for multiple comparisons in the GSEA: GRB2 events in ERBB2 signaling, for which 6 of 21 genes were BD associated (PFDR = 0.0377), and NCAM signaling for neurite out-growth, for which 11 out of 62 genes were BD associated (PFDR = 0.0451). Most pathway genes showed peaks of RNA co-expression during fetal development and infancy and mapped to neocortical areas and parts of the limbic system. Limitations: Pathway associations were technically reproduced by two methods, although they were not formally replicated in independent samples. Gene expression was explored in controls but not in patients. Conclusions: Pathway analysis in large GWAS data of BD and follow-up of gene expression patterns in healthy brains provide support for an involvement of neurodevelopmental processes in the etiology of this neuropsychiatric disease. Future studies are required to further evaluate the relevance of the implicated genes on pathway functioning and clinical aspects of BD. | ||
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650 | 4 | |a GRB2 events in ERBB2 signaling | |
650 | 4 | |a NCAM signaling for neurite out-growth | |
650 | 4 | |a Neurodevelopmental disorder | |
650 | 4 | |a Pathway analysis | |
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10.1016/j.jad.2017.11.068 doi (DE-627)1580279392 (DE-576)510279392 (DE-599)BSZ510279392 (OCoLC)1341017239 DE-627 ger DE-627 rda eng Mühleisen, Thomas W. 1975- verfasserin (DE-588)132121220 (DE-627)518146596 (DE-576)298955350 aut Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder Thomas W. Mühleisen, Céline S. Reinbold, Andreas J. Forstner, Lilia I. Abramova, Martin Alda, Gulja Babadjanova, Michael Bauer, Paul Brennan, Alexander Chuchalin, Cristiana Cruceanu, Piotr M. Czerski, Franziska Degenhardt, Sascha B. Fischer, Janice M. Fullerton, Scott D. Gordon, Maria Grigoroiu-Serbanescu, Paul Grof, Joanna Hauser, Martin Hautzinger, Stefan Herms, Per Hoffmann, Jutta Kammerer-Ciernioch, Elza Khusnutdinova, Manolis Kogevinas, Valery Krasnov, André Lacour, Catherine Laprise, Markus Leber, Jolanta Lissowska, Susanne Lucae, Anna Maaser, Wolfgang Maier, Nicholas G. Martin, Manuel Mattheisen, Fermin Mayoral, James D. McKay, Sarah E. Medland, Philip B. Mitchell, Susanne Moebus, Grant W. Montgomery, Bertram Müller-Myhsok, Lilijana Oruc, Galina Pantelejeva, Andrea Pfennig, Lejla Pojskic, Alexey Polonikov, Andreas Reif, Fabio Rivas, Guy A. Rouleau, Lorena M. Schenk, Peter R. Schofield, Markus Schwarz, Fabian Streit, Jana Strohmaier, Neonila Szeszenia-Dabrowska, Alexander S. Tiganov, Jens Treutlein, Gustavo Turecki, Helmut Vedder, Stephanie H. Witt, Thomas G. Schulze, Marcella Rietschel, Markus M. Nöthen, Sven Cichon 2018 6 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Available online: 14 November 2017 Gesehen am 22.08.2018 Background: Bipolar disorder (BD) is a common and highly heritable disorder of mood. Genome-wide association studies (GWAS) have identified several independent susceptibility loci. In order to extract more biological information from GWAS data, multi-locus approaches represent powerful tools since they utilize knowledge about biological processes to integrate functional sets of genes at strongly to moderately associated loci. Methods: We conducted gene set enrichment analyses (GSEA) using 2.3 million single-nucleotide polymorphisms, 397 Reactome pathways and 24,025 patients with BD and controls. RNA expression of implicated individual genes and gene sets were examined in post-mortem brains across lifespan. Results: Two pathways showed a significant enrichment after correction for multiple comparisons in the GSEA: GRB2 events in ERBB2 signaling, for which 6 of 21 genes were BD associated (PFDR = 0.0377), and NCAM signaling for neurite out-growth, for which 11 out of 62 genes were BD associated (PFDR = 0.0451). Most pathway genes showed peaks of RNA co-expression during fetal development and infancy and mapped to neocortical areas and parts of the limbic system. Limitations: Pathway associations were technically reproduced by two methods, although they were not formally replicated in independent samples. Gene expression was explored in controls but not in patients. Conclusions: Pathway analysis in large GWAS data of BD and follow-up of gene expression patterns in healthy brains provide support for an involvement of neurodevelopmental processes in the etiology of this neuropsychiatric disease. Future studies are required to further evaluate the relevance of the implicated genes on pathway functioning and clinical aspects of BD. 2017 Bipolar disorder GRB2 events in ERBB2 signaling NCAM signaling for neurite out-growth Neurodevelopmental disorder Pathway analysis Streit, Fabian 1982- verfasserin (DE-588)113749199X (DE-627)894689843 (DE-576)491387970 aut Strohmaier, Jana 1980- verfasserin (DE-588)103180157X (DE-627)73737103X (DE-576)379533588 aut Treutlein, Jens 1968- verfasserin (DE-588)1093438746 (DE-627)853501394 (DE-576)462705420 aut Witt, Stephanie 1970- verfasserin (DE-588)132177897 (DE-627)519022432 (DE-576)298988399 aut Rietschel, Marcella 1957- verfasserin (DE-588)112785751 (DE-627)505574020 (DE-576)289742307 aut Enthalten in Journal of affective disorders Amsterdam [u.a.] : Elsevier Science, 1979 228(2018), Seite 20-25 Online-Ressource (DE-627)306659670 (DE-600)1500487-9 (DE-576)081986327 1573-2517 nnns volume:228 year:2018 pages:20-25 extent:6 http://dx.doi.org/10.1016/j.jad.2017.11.068 Verlag Resolving-System Pay-per-use Volltext http://www.sciencedirect.com/science/article/pii/S0165032717315082 Verlag Pay-per-use Volltext GBV_USEFLAG_U GBV_ILN_2013 ISIL_DE-16-250 SYSFLAG_1 GBV_KXP SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 AR 228 2018 20-25 6 2013 01 DE-16-250 3022932863 00 --%%-- --%%-- --%%-- --%%-- l01 22-08-18 2013 01 DE-16-250 00 s hd2018 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_64 2013 01 DE-16-250 03 s s_6 2013 01 DE-16-250 04 p (DE-627)1551063484 Treutlein, Jens 2013 01 DE-16-250 04 k (DE-627)1416822720 Extern 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_57 2013 01 DE-16-250 05 p (DE-627)1572070226 Witt, Stephanie 2013 01 DE-16-250 05 k (DE-627)1416467254 Medizinische Fakultät Mannheim 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_60 2013 01 DE-16-250 06 p (DE-627)1447886461 Rietschel, Marcella 2013 01 DE-16-250 06 k (DE-627)1416467254 Medizinische Fakultät Mannheim 2013 01 DE-16-250 06 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 06 s pos_62 |
spelling |
10.1016/j.jad.2017.11.068 doi (DE-627)1580279392 (DE-576)510279392 (DE-599)BSZ510279392 (OCoLC)1341017239 DE-627 ger DE-627 rda eng Mühleisen, Thomas W. 1975- verfasserin (DE-588)132121220 (DE-627)518146596 (DE-576)298955350 aut Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder Thomas W. Mühleisen, Céline S. Reinbold, Andreas J. Forstner, Lilia I. Abramova, Martin Alda, Gulja Babadjanova, Michael Bauer, Paul Brennan, Alexander Chuchalin, Cristiana Cruceanu, Piotr M. Czerski, Franziska Degenhardt, Sascha B. Fischer, Janice M. Fullerton, Scott D. Gordon, Maria Grigoroiu-Serbanescu, Paul Grof, Joanna Hauser, Martin Hautzinger, Stefan Herms, Per Hoffmann, Jutta Kammerer-Ciernioch, Elza Khusnutdinova, Manolis Kogevinas, Valery Krasnov, André Lacour, Catherine Laprise, Markus Leber, Jolanta Lissowska, Susanne Lucae, Anna Maaser, Wolfgang Maier, Nicholas G. Martin, Manuel Mattheisen, Fermin Mayoral, James D. McKay, Sarah E. Medland, Philip B. Mitchell, Susanne Moebus, Grant W. Montgomery, Bertram Müller-Myhsok, Lilijana Oruc, Galina Pantelejeva, Andrea Pfennig, Lejla Pojskic, Alexey Polonikov, Andreas Reif, Fabio Rivas, Guy A. Rouleau, Lorena M. Schenk, Peter R. Schofield, Markus Schwarz, Fabian Streit, Jana Strohmaier, Neonila Szeszenia-Dabrowska, Alexander S. Tiganov, Jens Treutlein, Gustavo Turecki, Helmut Vedder, Stephanie H. Witt, Thomas G. Schulze, Marcella Rietschel, Markus M. Nöthen, Sven Cichon 2018 6 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Available online: 14 November 2017 Gesehen am 22.08.2018 Background: Bipolar disorder (BD) is a common and highly heritable disorder of mood. Genome-wide association studies (GWAS) have identified several independent susceptibility loci. In order to extract more biological information from GWAS data, multi-locus approaches represent powerful tools since they utilize knowledge about biological processes to integrate functional sets of genes at strongly to moderately associated loci. Methods: We conducted gene set enrichment analyses (GSEA) using 2.3 million single-nucleotide polymorphisms, 397 Reactome pathways and 24,025 patients with BD and controls. RNA expression of implicated individual genes and gene sets were examined in post-mortem brains across lifespan. Results: Two pathways showed a significant enrichment after correction for multiple comparisons in the GSEA: GRB2 events in ERBB2 signaling, for which 6 of 21 genes were BD associated (PFDR = 0.0377), and NCAM signaling for neurite out-growth, for which 11 out of 62 genes were BD associated (PFDR = 0.0451). Most pathway genes showed peaks of RNA co-expression during fetal development and infancy and mapped to neocortical areas and parts of the limbic system. Limitations: Pathway associations were technically reproduced by two methods, although they were not formally replicated in independent samples. Gene expression was explored in controls but not in patients. Conclusions: Pathway analysis in large GWAS data of BD and follow-up of gene expression patterns in healthy brains provide support for an involvement of neurodevelopmental processes in the etiology of this neuropsychiatric disease. Future studies are required to further evaluate the relevance of the implicated genes on pathway functioning and clinical aspects of BD. 2017 Bipolar disorder GRB2 events in ERBB2 signaling NCAM signaling for neurite out-growth Neurodevelopmental disorder Pathway analysis Streit, Fabian 1982- verfasserin (DE-588)113749199X (DE-627)894689843 (DE-576)491387970 aut Strohmaier, Jana 1980- verfasserin (DE-588)103180157X (DE-627)73737103X (DE-576)379533588 aut Treutlein, Jens 1968- verfasserin (DE-588)1093438746 (DE-627)853501394 (DE-576)462705420 aut Witt, Stephanie 1970- verfasserin (DE-588)132177897 (DE-627)519022432 (DE-576)298988399 aut Rietschel, Marcella 1957- verfasserin (DE-588)112785751 (DE-627)505574020 (DE-576)289742307 aut Enthalten in Journal of affective disorders Amsterdam [u.a.] : Elsevier Science, 1979 228(2018), Seite 20-25 Online-Ressource (DE-627)306659670 (DE-600)1500487-9 (DE-576)081986327 1573-2517 nnns volume:228 year:2018 pages:20-25 extent:6 http://dx.doi.org/10.1016/j.jad.2017.11.068 Verlag Resolving-System Pay-per-use Volltext http://www.sciencedirect.com/science/article/pii/S0165032717315082 Verlag Pay-per-use Volltext GBV_USEFLAG_U GBV_ILN_2013 ISIL_DE-16-250 SYSFLAG_1 GBV_KXP SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 AR 228 2018 20-25 6 2013 01 DE-16-250 3022932863 00 --%%-- --%%-- --%%-- --%%-- l01 22-08-18 2013 01 DE-16-250 00 s hd2018 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_64 2013 01 DE-16-250 03 s s_6 2013 01 DE-16-250 04 p (DE-627)1551063484 Treutlein, Jens 2013 01 DE-16-250 04 k (DE-627)1416822720 Extern 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_57 2013 01 DE-16-250 05 p (DE-627)1572070226 Witt, Stephanie 2013 01 DE-16-250 05 k (DE-627)1416467254 Medizinische Fakultät Mannheim 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_60 2013 01 DE-16-250 06 p (DE-627)1447886461 Rietschel, Marcella 2013 01 DE-16-250 06 k (DE-627)1416467254 Medizinische Fakultät Mannheim 2013 01 DE-16-250 06 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 06 s pos_62 |
allfields_unstemmed |
10.1016/j.jad.2017.11.068 doi (DE-627)1580279392 (DE-576)510279392 (DE-599)BSZ510279392 (OCoLC)1341017239 DE-627 ger DE-627 rda eng Mühleisen, Thomas W. 1975- verfasserin (DE-588)132121220 (DE-627)518146596 (DE-576)298955350 aut Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder Thomas W. Mühleisen, Céline S. Reinbold, Andreas J. Forstner, Lilia I. Abramova, Martin Alda, Gulja Babadjanova, Michael Bauer, Paul Brennan, Alexander Chuchalin, Cristiana Cruceanu, Piotr M. Czerski, Franziska Degenhardt, Sascha B. Fischer, Janice M. Fullerton, Scott D. Gordon, Maria Grigoroiu-Serbanescu, Paul Grof, Joanna Hauser, Martin Hautzinger, Stefan Herms, Per Hoffmann, Jutta Kammerer-Ciernioch, Elza Khusnutdinova, Manolis Kogevinas, Valery Krasnov, André Lacour, Catherine Laprise, Markus Leber, Jolanta Lissowska, Susanne Lucae, Anna Maaser, Wolfgang Maier, Nicholas G. Martin, Manuel Mattheisen, Fermin Mayoral, James D. McKay, Sarah E. Medland, Philip B. Mitchell, Susanne Moebus, Grant W. Montgomery, Bertram Müller-Myhsok, Lilijana Oruc, Galina Pantelejeva, Andrea Pfennig, Lejla Pojskic, Alexey Polonikov, Andreas Reif, Fabio Rivas, Guy A. Rouleau, Lorena M. Schenk, Peter R. Schofield, Markus Schwarz, Fabian Streit, Jana Strohmaier, Neonila Szeszenia-Dabrowska, Alexander S. Tiganov, Jens Treutlein, Gustavo Turecki, Helmut Vedder, Stephanie H. Witt, Thomas G. Schulze, Marcella Rietschel, Markus M. Nöthen, Sven Cichon 2018 6 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Available online: 14 November 2017 Gesehen am 22.08.2018 Background: Bipolar disorder (BD) is a common and highly heritable disorder of mood. Genome-wide association studies (GWAS) have identified several independent susceptibility loci. In order to extract more biological information from GWAS data, multi-locus approaches represent powerful tools since they utilize knowledge about biological processes to integrate functional sets of genes at strongly to moderately associated loci. Methods: We conducted gene set enrichment analyses (GSEA) using 2.3 million single-nucleotide polymorphisms, 397 Reactome pathways and 24,025 patients with BD and controls. RNA expression of implicated individual genes and gene sets were examined in post-mortem brains across lifespan. Results: Two pathways showed a significant enrichment after correction for multiple comparisons in the GSEA: GRB2 events in ERBB2 signaling, for which 6 of 21 genes were BD associated (PFDR = 0.0377), and NCAM signaling for neurite out-growth, for which 11 out of 62 genes were BD associated (PFDR = 0.0451). Most pathway genes showed peaks of RNA co-expression during fetal development and infancy and mapped to neocortical areas and parts of the limbic system. Limitations: Pathway associations were technically reproduced by two methods, although they were not formally replicated in independent samples. Gene expression was explored in controls but not in patients. Conclusions: Pathway analysis in large GWAS data of BD and follow-up of gene expression patterns in healthy brains provide support for an involvement of neurodevelopmental processes in the etiology of this neuropsychiatric disease. Future studies are required to further evaluate the relevance of the implicated genes on pathway functioning and clinical aspects of BD. 2017 Bipolar disorder GRB2 events in ERBB2 signaling NCAM signaling for neurite out-growth Neurodevelopmental disorder Pathway analysis Streit, Fabian 1982- verfasserin (DE-588)113749199X (DE-627)894689843 (DE-576)491387970 aut Strohmaier, Jana 1980- verfasserin (DE-588)103180157X (DE-627)73737103X (DE-576)379533588 aut Treutlein, Jens 1968- verfasserin (DE-588)1093438746 (DE-627)853501394 (DE-576)462705420 aut Witt, Stephanie 1970- verfasserin (DE-588)132177897 (DE-627)519022432 (DE-576)298988399 aut Rietschel, Marcella 1957- verfasserin (DE-588)112785751 (DE-627)505574020 (DE-576)289742307 aut Enthalten in Journal of affective disorders Amsterdam [u.a.] : Elsevier Science, 1979 228(2018), Seite 20-25 Online-Ressource (DE-627)306659670 (DE-600)1500487-9 (DE-576)081986327 1573-2517 nnns volume:228 year:2018 pages:20-25 extent:6 http://dx.doi.org/10.1016/j.jad.2017.11.068 Verlag Resolving-System Pay-per-use Volltext http://www.sciencedirect.com/science/article/pii/S0165032717315082 Verlag Pay-per-use Volltext GBV_USEFLAG_U GBV_ILN_2013 ISIL_DE-16-250 SYSFLAG_1 GBV_KXP SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 AR 228 2018 20-25 6 2013 01 DE-16-250 3022932863 00 --%%-- --%%-- --%%-- --%%-- l01 22-08-18 2013 01 DE-16-250 00 s hd2018 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_64 2013 01 DE-16-250 03 s s_6 2013 01 DE-16-250 04 p (DE-627)1551063484 Treutlein, Jens 2013 01 DE-16-250 04 k (DE-627)1416822720 Extern 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_57 2013 01 DE-16-250 05 p (DE-627)1572070226 Witt, Stephanie 2013 01 DE-16-250 05 k (DE-627)1416467254 Medizinische Fakultät Mannheim 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_60 2013 01 DE-16-250 06 p (DE-627)1447886461 Rietschel, Marcella 2013 01 DE-16-250 06 k (DE-627)1416467254 Medizinische Fakultät Mannheim 2013 01 DE-16-250 06 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 06 s pos_62 |
allfieldsGer |
10.1016/j.jad.2017.11.068 doi (DE-627)1580279392 (DE-576)510279392 (DE-599)BSZ510279392 (OCoLC)1341017239 DE-627 ger DE-627 rda eng Mühleisen, Thomas W. 1975- verfasserin (DE-588)132121220 (DE-627)518146596 (DE-576)298955350 aut Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder Thomas W. Mühleisen, Céline S. Reinbold, Andreas J. Forstner, Lilia I. Abramova, Martin Alda, Gulja Babadjanova, Michael Bauer, Paul Brennan, Alexander Chuchalin, Cristiana Cruceanu, Piotr M. Czerski, Franziska Degenhardt, Sascha B. Fischer, Janice M. Fullerton, Scott D. Gordon, Maria Grigoroiu-Serbanescu, Paul Grof, Joanna Hauser, Martin Hautzinger, Stefan Herms, Per Hoffmann, Jutta Kammerer-Ciernioch, Elza Khusnutdinova, Manolis Kogevinas, Valery Krasnov, André Lacour, Catherine Laprise, Markus Leber, Jolanta Lissowska, Susanne Lucae, Anna Maaser, Wolfgang Maier, Nicholas G. Martin, Manuel Mattheisen, Fermin Mayoral, James D. McKay, Sarah E. Medland, Philip B. Mitchell, Susanne Moebus, Grant W. Montgomery, Bertram Müller-Myhsok, Lilijana Oruc, Galina Pantelejeva, Andrea Pfennig, Lejla Pojskic, Alexey Polonikov, Andreas Reif, Fabio Rivas, Guy A. Rouleau, Lorena M. Schenk, Peter R. Schofield, Markus Schwarz, Fabian Streit, Jana Strohmaier, Neonila Szeszenia-Dabrowska, Alexander S. Tiganov, Jens Treutlein, Gustavo Turecki, Helmut Vedder, Stephanie H. Witt, Thomas G. Schulze, Marcella Rietschel, Markus M. Nöthen, Sven Cichon 2018 6 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Available online: 14 November 2017 Gesehen am 22.08.2018 Background: Bipolar disorder (BD) is a common and highly heritable disorder of mood. Genome-wide association studies (GWAS) have identified several independent susceptibility loci. In order to extract more biological information from GWAS data, multi-locus approaches represent powerful tools since they utilize knowledge about biological processes to integrate functional sets of genes at strongly to moderately associated loci. Methods: We conducted gene set enrichment analyses (GSEA) using 2.3 million single-nucleotide polymorphisms, 397 Reactome pathways and 24,025 patients with BD and controls. RNA expression of implicated individual genes and gene sets were examined in post-mortem brains across lifespan. Results: Two pathways showed a significant enrichment after correction for multiple comparisons in the GSEA: GRB2 events in ERBB2 signaling, for which 6 of 21 genes were BD associated (PFDR = 0.0377), and NCAM signaling for neurite out-growth, for which 11 out of 62 genes were BD associated (PFDR = 0.0451). Most pathway genes showed peaks of RNA co-expression during fetal development and infancy and mapped to neocortical areas and parts of the limbic system. Limitations: Pathway associations were technically reproduced by two methods, although they were not formally replicated in independent samples. Gene expression was explored in controls but not in patients. Conclusions: Pathway analysis in large GWAS data of BD and follow-up of gene expression patterns in healthy brains provide support for an involvement of neurodevelopmental processes in the etiology of this neuropsychiatric disease. Future studies are required to further evaluate the relevance of the implicated genes on pathway functioning and clinical aspects of BD. 2017 Bipolar disorder GRB2 events in ERBB2 signaling NCAM signaling for neurite out-growth Neurodevelopmental disorder Pathway analysis Streit, Fabian 1982- verfasserin (DE-588)113749199X (DE-627)894689843 (DE-576)491387970 aut Strohmaier, Jana 1980- verfasserin (DE-588)103180157X (DE-627)73737103X (DE-576)379533588 aut Treutlein, Jens 1968- verfasserin (DE-588)1093438746 (DE-627)853501394 (DE-576)462705420 aut Witt, Stephanie 1970- verfasserin (DE-588)132177897 (DE-627)519022432 (DE-576)298988399 aut Rietschel, Marcella 1957- verfasserin (DE-588)112785751 (DE-627)505574020 (DE-576)289742307 aut Enthalten in Journal of affective disorders Amsterdam [u.a.] : Elsevier Science, 1979 228(2018), Seite 20-25 Online-Ressource (DE-627)306659670 (DE-600)1500487-9 (DE-576)081986327 1573-2517 nnns volume:228 year:2018 pages:20-25 extent:6 http://dx.doi.org/10.1016/j.jad.2017.11.068 Verlag Resolving-System Pay-per-use Volltext http://www.sciencedirect.com/science/article/pii/S0165032717315082 Verlag Pay-per-use Volltext GBV_USEFLAG_U GBV_ILN_2013 ISIL_DE-16-250 SYSFLAG_1 GBV_KXP SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 AR 228 2018 20-25 6 2013 01 DE-16-250 3022932863 00 --%%-- --%%-- --%%-- --%%-- l01 22-08-18 2013 01 DE-16-250 00 s hd2018 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_64 2013 01 DE-16-250 03 s s_6 2013 01 DE-16-250 04 p (DE-627)1551063484 Treutlein, Jens 2013 01 DE-16-250 04 k (DE-627)1416822720 Extern 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_57 2013 01 DE-16-250 05 p (DE-627)1572070226 Witt, Stephanie 2013 01 DE-16-250 05 k (DE-627)1416467254 Medizinische Fakultät Mannheim 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_60 2013 01 DE-16-250 06 p (DE-627)1447886461 Rietschel, Marcella 2013 01 DE-16-250 06 k (DE-627)1416467254 Medizinische Fakultät Mannheim 2013 01 DE-16-250 06 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 06 s pos_62 |
allfieldsSound |
10.1016/j.jad.2017.11.068 doi (DE-627)1580279392 (DE-576)510279392 (DE-599)BSZ510279392 (OCoLC)1341017239 DE-627 ger DE-627 rda eng Mühleisen, Thomas W. 1975- verfasserin (DE-588)132121220 (DE-627)518146596 (DE-576)298955350 aut Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder Thomas W. Mühleisen, Céline S. Reinbold, Andreas J. Forstner, Lilia I. Abramova, Martin Alda, Gulja Babadjanova, Michael Bauer, Paul Brennan, Alexander Chuchalin, Cristiana Cruceanu, Piotr M. Czerski, Franziska Degenhardt, Sascha B. Fischer, Janice M. Fullerton, Scott D. Gordon, Maria Grigoroiu-Serbanescu, Paul Grof, Joanna Hauser, Martin Hautzinger, Stefan Herms, Per Hoffmann, Jutta Kammerer-Ciernioch, Elza Khusnutdinova, Manolis Kogevinas, Valery Krasnov, André Lacour, Catherine Laprise, Markus Leber, Jolanta Lissowska, Susanne Lucae, Anna Maaser, Wolfgang Maier, Nicholas G. Martin, Manuel Mattheisen, Fermin Mayoral, James D. McKay, Sarah E. Medland, Philip B. Mitchell, Susanne Moebus, Grant W. Montgomery, Bertram Müller-Myhsok, Lilijana Oruc, Galina Pantelejeva, Andrea Pfennig, Lejla Pojskic, Alexey Polonikov, Andreas Reif, Fabio Rivas, Guy A. Rouleau, Lorena M. Schenk, Peter R. Schofield, Markus Schwarz, Fabian Streit, Jana Strohmaier, Neonila Szeszenia-Dabrowska, Alexander S. Tiganov, Jens Treutlein, Gustavo Turecki, Helmut Vedder, Stephanie H. Witt, Thomas G. Schulze, Marcella Rietschel, Markus M. Nöthen, Sven Cichon 2018 6 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Available online: 14 November 2017 Gesehen am 22.08.2018 Background: Bipolar disorder (BD) is a common and highly heritable disorder of mood. Genome-wide association studies (GWAS) have identified several independent susceptibility loci. In order to extract more biological information from GWAS data, multi-locus approaches represent powerful tools since they utilize knowledge about biological processes to integrate functional sets of genes at strongly to moderately associated loci. Methods: We conducted gene set enrichment analyses (GSEA) using 2.3 million single-nucleotide polymorphisms, 397 Reactome pathways and 24,025 patients with BD and controls. RNA expression of implicated individual genes and gene sets were examined in post-mortem brains across lifespan. Results: Two pathways showed a significant enrichment after correction for multiple comparisons in the GSEA: GRB2 events in ERBB2 signaling, for which 6 of 21 genes were BD associated (PFDR = 0.0377), and NCAM signaling for neurite out-growth, for which 11 out of 62 genes were BD associated (PFDR = 0.0451). Most pathway genes showed peaks of RNA co-expression during fetal development and infancy and mapped to neocortical areas and parts of the limbic system. Limitations: Pathway associations were technically reproduced by two methods, although they were not formally replicated in independent samples. Gene expression was explored in controls but not in patients. Conclusions: Pathway analysis in large GWAS data of BD and follow-up of gene expression patterns in healthy brains provide support for an involvement of neurodevelopmental processes in the etiology of this neuropsychiatric disease. Future studies are required to further evaluate the relevance of the implicated genes on pathway functioning and clinical aspects of BD. 2017 Bipolar disorder GRB2 events in ERBB2 signaling NCAM signaling for neurite out-growth Neurodevelopmental disorder Pathway analysis Streit, Fabian 1982- verfasserin (DE-588)113749199X (DE-627)894689843 (DE-576)491387970 aut Strohmaier, Jana 1980- verfasserin (DE-588)103180157X (DE-627)73737103X (DE-576)379533588 aut Treutlein, Jens 1968- verfasserin (DE-588)1093438746 (DE-627)853501394 (DE-576)462705420 aut Witt, Stephanie 1970- verfasserin (DE-588)132177897 (DE-627)519022432 (DE-576)298988399 aut Rietschel, Marcella 1957- verfasserin (DE-588)112785751 (DE-627)505574020 (DE-576)289742307 aut Enthalten in Journal of affective disorders Amsterdam [u.a.] : Elsevier Science, 1979 228(2018), Seite 20-25 Online-Ressource (DE-627)306659670 (DE-600)1500487-9 (DE-576)081986327 1573-2517 nnns volume:228 year:2018 pages:20-25 extent:6 http://dx.doi.org/10.1016/j.jad.2017.11.068 Verlag Resolving-System Pay-per-use Volltext http://www.sciencedirect.com/science/article/pii/S0165032717315082 Verlag Pay-per-use Volltext GBV_USEFLAG_U GBV_ILN_2013 ISIL_DE-16-250 SYSFLAG_1 GBV_KXP SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 AR 228 2018 20-25 6 2013 01 DE-16-250 3022932863 00 --%%-- --%%-- --%%-- --%%-- l01 22-08-18 2013 01 DE-16-250 00 s hd2018 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_64 2013 01 DE-16-250 03 s s_6 2013 01 DE-16-250 04 p (DE-627)1551063484 Treutlein, Jens 2013 01 DE-16-250 04 k (DE-627)1416822720 Extern 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_57 2013 01 DE-16-250 05 p (DE-627)1572070226 Witt, Stephanie 2013 01 DE-16-250 05 k (DE-627)1416467254 Medizinische Fakultät Mannheim 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_60 2013 01 DE-16-250 06 p (DE-627)1447886461 Rietschel, Marcella 2013 01 DE-16-250 06 k (DE-627)1416467254 Medizinische Fakultät Mannheim 2013 01 DE-16-250 06 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 06 s pos_62 |
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Enthalten in Journal of affective disorders 228(2018), Seite 20-25 volume:228 year:2018 pages:20-25 extent:6 |
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Mühleisen, Thomas W. @@aut@@ Streit, Fabian @@aut@@ Strohmaier, Jana @@aut@@ Treutlein, Jens @@aut@@ Witt, Stephanie @@aut@@ Rietschel, Marcella @@aut@@ |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a2200265 4500</leader><controlfield tag="001">1580279392</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230427065653.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">180822r20182017xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.jad.2017.11.068</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)1580279392</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-576)510279392</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)BSZ510279392</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(OCoLC)1341017239</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rda</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Mühleisen, Thomas W.</subfield><subfield code="d">1975-</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(DE-588)132121220</subfield><subfield code="0">(DE-627)518146596</subfield><subfield code="0">(DE-576)298955350</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder</subfield><subfield code="c">Thomas W. Mühleisen, Céline S. Reinbold, Andreas J. Forstner, Lilia I. Abramova, Martin Alda, Gulja Babadjanova, Michael Bauer, Paul Brennan, Alexander Chuchalin, Cristiana Cruceanu, Piotr M. Czerski, Franziska Degenhardt, Sascha B. Fischer, Janice M. Fullerton, Scott D. Gordon, Maria Grigoroiu-Serbanescu, Paul Grof, Joanna Hauser, Martin Hautzinger, Stefan Herms, Per Hoffmann, Jutta Kammerer-Ciernioch, Elza Khusnutdinova, Manolis Kogevinas, Valery Krasnov, André Lacour, Catherine Laprise, Markus Leber, Jolanta Lissowska, Susanne Lucae, Anna Maaser, Wolfgang Maier, Nicholas G. Martin, Manuel Mattheisen, Fermin Mayoral, James D. McKay, Sarah E. Medland, Philip B. Mitchell, Susanne Moebus, Grant W. Montgomery, Bertram Müller-Myhsok, Lilijana Oruc, Galina Pantelejeva, Andrea Pfennig, Lejla Pojskic, Alexey Polonikov, Andreas Reif, Fabio Rivas, Guy A. Rouleau, Lorena M. Schenk, Peter R. Schofield, Markus Schwarz, Fabian Streit, Jana Strohmaier, Neonila Szeszenia-Dabrowska, Alexander S. Tiganov, Jens Treutlein, Gustavo Turecki, Helmut Vedder, Stephanie H. Witt, Thomas G. Schulze, Marcella Rietschel, Markus M. Nöthen, Sven Cichon</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2018</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">6</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">Available online: 14 November 2017</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">Gesehen am 22.08.2018</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background: Bipolar disorder (BD) is a common and highly heritable disorder of mood. Genome-wide association studies (GWAS) have identified several independent susceptibility loci. In order to extract more biological information from GWAS data, multi-locus approaches represent powerful tools since they utilize knowledge about biological processes to integrate functional sets of genes at strongly to moderately associated loci. Methods: We conducted gene set enrichment analyses (GSEA) using 2.3 million single-nucleotide polymorphisms, 397 Reactome pathways and 24,025 patients with BD and controls. RNA expression of implicated individual genes and gene sets were examined in post-mortem brains across lifespan. Results: Two pathways showed a significant enrichment after correction for multiple comparisons in the GSEA: GRB2 events in ERBB2 signaling, for which 6 of 21 genes were BD associated (PFDR = 0.0377), and NCAM signaling for neurite out-growth, for which 11 out of 62 genes were BD associated (PFDR = 0.0451). 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Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder Thomas W. Mühleisen, Céline S. Reinbold, Andreas J. Forstner, Lilia I. Abramova, Martin Alda, Gulja Babadjanova, Michael Bauer, Paul Brennan, Alexander Chuchalin, Cristiana Cruceanu, Piotr M. Czerski, Franziska Degenhardt, Sascha B. Fischer, Janice M. Fullerton, Scott D. Gordon, Maria Grigoroiu-Serbanescu, Paul Grof, Joanna Hauser, Martin Hautzinger, Stefan Herms, Per Hoffmann, Jutta Kammerer-Ciernioch, Elza Khusnutdinova, Manolis Kogevinas, Valery Krasnov, André Lacour, Catherine Laprise, Markus Leber, Jolanta Lissowska, Susanne Lucae, Anna Maaser, Wolfgang Maier, Nicholas G. Martin, Manuel Mattheisen, Fermin Mayoral, James D. McKay, Sarah E. Medland, Philip B. Mitchell, Susanne Moebus, Grant W. Montgomery, Bertram Müller-Myhsok, Lilijana Oruc, Galina Pantelejeva, Andrea Pfennig, Lejla Pojskic, Alexey Polonikov, Andreas Reif, Fabio Rivas, Guy A. Rouleau, Lorena M. Schenk, Peter R. Schofield, Markus Schwarz, Fabian Streit, Jana Strohmaier, Neonila Szeszenia-Dabrowska, Alexander S. Tiganov, Jens Treutlein, Gustavo Turecki, Helmut Vedder, Stephanie H. Witt, Thomas G. Schulze, Marcella Rietschel, Markus M. Nöthen, Sven Cichon |
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gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder |
title_auth |
Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder |
abstract |
Background: Bipolar disorder (BD) is a common and highly heritable disorder of mood. Genome-wide association studies (GWAS) have identified several independent susceptibility loci. In order to extract more biological information from GWAS data, multi-locus approaches represent powerful tools since they utilize knowledge about biological processes to integrate functional sets of genes at strongly to moderately associated loci. Methods: We conducted gene set enrichment analyses (GSEA) using 2.3 million single-nucleotide polymorphisms, 397 Reactome pathways and 24,025 patients with BD and controls. RNA expression of implicated individual genes and gene sets were examined in post-mortem brains across lifespan. Results: Two pathways showed a significant enrichment after correction for multiple comparisons in the GSEA: GRB2 events in ERBB2 signaling, for which 6 of 21 genes were BD associated (PFDR = 0.0377), and NCAM signaling for neurite out-growth, for which 11 out of 62 genes were BD associated (PFDR = 0.0451). Most pathway genes showed peaks of RNA co-expression during fetal development and infancy and mapped to neocortical areas and parts of the limbic system. Limitations: Pathway associations were technically reproduced by two methods, although they were not formally replicated in independent samples. Gene expression was explored in controls but not in patients. Conclusions: Pathway analysis in large GWAS data of BD and follow-up of gene expression patterns in healthy brains provide support for an involvement of neurodevelopmental processes in the etiology of this neuropsychiatric disease. Future studies are required to further evaluate the relevance of the implicated genes on pathway functioning and clinical aspects of BD. Available online: 14 November 2017 Gesehen am 22.08.2018 |
abstractGer |
Background: Bipolar disorder (BD) is a common and highly heritable disorder of mood. Genome-wide association studies (GWAS) have identified several independent susceptibility loci. In order to extract more biological information from GWAS data, multi-locus approaches represent powerful tools since they utilize knowledge about biological processes to integrate functional sets of genes at strongly to moderately associated loci. Methods: We conducted gene set enrichment analyses (GSEA) using 2.3 million single-nucleotide polymorphisms, 397 Reactome pathways and 24,025 patients with BD and controls. RNA expression of implicated individual genes and gene sets were examined in post-mortem brains across lifespan. Results: Two pathways showed a significant enrichment after correction for multiple comparisons in the GSEA: GRB2 events in ERBB2 signaling, for which 6 of 21 genes were BD associated (PFDR = 0.0377), and NCAM signaling for neurite out-growth, for which 11 out of 62 genes were BD associated (PFDR = 0.0451). Most pathway genes showed peaks of RNA co-expression during fetal development and infancy and mapped to neocortical areas and parts of the limbic system. Limitations: Pathway associations were technically reproduced by two methods, although they were not formally replicated in independent samples. Gene expression was explored in controls but not in patients. Conclusions: Pathway analysis in large GWAS data of BD and follow-up of gene expression patterns in healthy brains provide support for an involvement of neurodevelopmental processes in the etiology of this neuropsychiatric disease. Future studies are required to further evaluate the relevance of the implicated genes on pathway functioning and clinical aspects of BD. Available online: 14 November 2017 Gesehen am 22.08.2018 |
abstract_unstemmed |
Background: Bipolar disorder (BD) is a common and highly heritable disorder of mood. Genome-wide association studies (GWAS) have identified several independent susceptibility loci. In order to extract more biological information from GWAS data, multi-locus approaches represent powerful tools since they utilize knowledge about biological processes to integrate functional sets of genes at strongly to moderately associated loci. Methods: We conducted gene set enrichment analyses (GSEA) using 2.3 million single-nucleotide polymorphisms, 397 Reactome pathways and 24,025 patients with BD and controls. RNA expression of implicated individual genes and gene sets were examined in post-mortem brains across lifespan. Results: Two pathways showed a significant enrichment after correction for multiple comparisons in the GSEA: GRB2 events in ERBB2 signaling, for which 6 of 21 genes were BD associated (PFDR = 0.0377), and NCAM signaling for neurite out-growth, for which 11 out of 62 genes were BD associated (PFDR = 0.0451). Most pathway genes showed peaks of RNA co-expression during fetal development and infancy and mapped to neocortical areas and parts of the limbic system. Limitations: Pathway associations were technically reproduced by two methods, although they were not formally replicated in independent samples. Gene expression was explored in controls but not in patients. Conclusions: Pathway analysis in large GWAS data of BD and follow-up of gene expression patterns in healthy brains provide support for an involvement of neurodevelopmental processes in the etiology of this neuropsychiatric disease. Future studies are required to further evaluate the relevance of the implicated genes on pathway functioning and clinical aspects of BD. Available online: 14 November 2017 Gesehen am 22.08.2018 |
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title_short |
Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder |
url |
http://dx.doi.org/10.1016/j.jad.2017.11.068 http://www.sciencedirect.com/science/article/pii/S0165032717315082 |
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Mühleisen, Thomas Walter Mühleisen, Thomas W. Streit, Fabian Emanuel Streit, Fabian Strohmaier, J. Strohmaier, Jana Treutlein, Jens Witt, S. H. Witt, Stephanie H. Witt, S. Witt, Stephanie Michel, Marcella Rietschel, Marcela D. C. Rietschel, M. Rietschel, Marcela Rietschel, Marcella |
GND_txt_mv |
Mühleisen, Thomas Walter Mühleisen, Thomas W. Streit, Fabian Emanuel Streit, Fabian Strohmaier, J. Strohmaier, Jana Treutlein, Jens Witt, S. H. Witt, Stephanie H. Witt, S. Witt, Stephanie Michel, Marcella Rietschel, Marcela D. C. Rietschel, M. Rietschel, Marcela Rietschel, Marcella |
GND_txtF_mv |
Mühleisen, Thomas Walter Mühleisen, Thomas W. Streit, Fabian Emanuel Streit, Fabian Strohmaier, J. Strohmaier, Jana Treutlein, Jens Witt, S. H. Witt, Stephanie H. Witt, S. Witt, Stephanie Michel, Marcella Rietschel, Marcela D. C. Rietschel, M. Rietschel, Marcela Rietschel, Marcella |
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callnumber-a |
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up_date |
2024-07-04T14:28:03.518Z |
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Genome-wide association studies (GWAS) have identified several independent susceptibility loci. In order to extract more biological information from GWAS data, multi-locus approaches represent powerful tools since they utilize knowledge about biological processes to integrate functional sets of genes at strongly to moderately associated loci. Methods: We conducted gene set enrichment analyses (GSEA) using 2.3 million single-nucleotide polymorphisms, 397 Reactome pathways and 24,025 patients with BD and controls. RNA expression of implicated individual genes and gene sets were examined in post-mortem brains across lifespan. Results: Two pathways showed a significant enrichment after correction for multiple comparisons in the GSEA: GRB2 events in ERBB2 signaling, for which 6 of 21 genes were BD associated (PFDR = 0.0377), and NCAM signaling for neurite out-growth, for which 11 out of 62 genes were BD associated (PFDR = 0.0451). 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