Manuel Mattheisen

Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder

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Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder. / Mühleisen, Thomas W.; Reinbold, Céline S.; Forstner, Andreas J.; Abramova, Lilia I.; Alda, Martin; Babadjanova, Gulja; Bauer, Michael; Brennan, Paul; Chuchalin, Alexander; Cruceanu, Cristiana; Czerski, Piotr M.; Degenhardt, Franziska; Fischer, Sascha B.; Fullerton, Janice M.; Gordon, Scott D.; Grigoroiu-Serbanescu, Maria; Grof, Paul; Hauser, Joanna; Hautzinger, Martin; Herms, Stefan; Hoffmann, Per; Kammerer-Ciernioch, Jutta; Khusnutdinova, Elza; Kogevinas, Manolis; Krasnov, Valery; Lacour, André; Laprise, Catherine; Leber, Markus; Lissowska, Jolanta; Lucae, Susanne; Maaser, Anna; Maier, Wolfgang; Martin, Nicholas G.; Mattheisen, Manuel; Mayoral, Fermin; McKay, James D.; Medland, Sarah E.; Mitchell, Philip B.; Moebus, Susanne; Montgomery, Grant W.; Müller-Myhsok, Bertram; Oruc, Lilijana; Pantelejeva, Galina; Pfennig, Andrea; Pojskic, Lejla; Polonikov, Alexey; Reif, Andreas; Rivas, Fabio; Rouleau, Guy A.; Schenk, Lorena M.; Schofield, Peter R.; Schwarz, Markus; Streit, Fabian; Strohmaier, Jana; Szeszenia-Dabrowska, Neonila; Tiganov, Alexander S.; Treutlein, Jens; Turecki, Gustavo; Vedder, Helmut; Witt, Stephanie H.; Schulze, Thomas G.; Rietschel, Marcella; Nöthen, Markus M.; Cichon, Sven.

In: Journal of Affective Disorders, Vol. 228, 01.03.2018, p. 20-25.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Mühleisen, TW, Reinbold, CS, Forstner, AJ, Abramova, LI, Alda, M, Babadjanova, G, Bauer, M, Brennan, P, Chuchalin, A, Cruceanu, C, Czerski, PM, Degenhardt, F, Fischer, SB, Fullerton, JM, Gordon, SD, Grigoroiu-Serbanescu, M, Grof, P, Hauser, J, Hautzinger, M, Herms, S, Hoffmann, P, Kammerer-Ciernioch, J, Khusnutdinova, E, Kogevinas, M, Krasnov, V, Lacour, A, Laprise, C, Leber, M, Lissowska, J, Lucae, S, Maaser, A, Maier, W, Martin, NG, Mattheisen, M, Mayoral, F, McKay, JD, Medland, SE, Mitchell, PB, Moebus, S, Montgomery, GW, Müller-Myhsok, B, Oruc, L, Pantelejeva, G, Pfennig, A, Pojskic, L, Polonikov, A, Reif, A, Rivas, F, Rouleau, GA, Schenk, LM, Schofield, PR, Schwarz, M, Streit, F, Strohmaier, J, Szeszenia-Dabrowska, N, Tiganov, AS, Treutlein, J, Turecki, G, Vedder, H, Witt, SH, Schulze, TG, Rietschel, M, Nöthen, MM & Cichon, S 2018, 'Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder', Journal of Affective Disorders, vol. 228, pp. 20-25. https://doi.org/10.1016/j.jad.2017.11.068

APA

Mühleisen, T. W., Reinbold, C. S., Forstner, A. J., Abramova, L. I., Alda, M., Babadjanova, G., Bauer, M., Brennan, P., Chuchalin, A., Cruceanu, C., Czerski, P. M., Degenhardt, F., Fischer, S. B., Fullerton, J. M., Gordon, S. D., Grigoroiu-Serbanescu, M., Grof, P., Hauser, J., Hautzinger, M., ... Cichon, S. (2018). Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder. Journal of Affective Disorders, 228, 20-25. https://doi.org/10.1016/j.jad.2017.11.068

CBE

Mühleisen TW, Reinbold CS, Forstner AJ, Abramova LI, Alda M, Babadjanova G, Bauer M, Brennan P, Chuchalin A, Cruceanu C, Czerski PM, Degenhardt F, Fischer SB, Fullerton JM, Gordon SD, Grigoroiu-Serbanescu M, Grof P, Hauser J, Hautzinger M, Herms S, Hoffmann P, Kammerer-Ciernioch J, Khusnutdinova E, Kogevinas M, Krasnov V, Lacour A, Laprise C, Leber M, Lissowska J, Lucae S, Maaser A, Maier W, Martin NG, Mattheisen M, Mayoral F, McKay JD, Medland SE, Mitchell PB, Moebus S, Montgomery GW, Müller-Myhsok B, Oruc L, Pantelejeva G, Pfennig A, Pojskic L, Polonikov A, Reif A, Rivas F, Rouleau GA, Schenk LM, Schofield PR, Schwarz M, Streit F, Strohmaier J, Szeszenia-Dabrowska N, Tiganov AS, Treutlein J, Turecki G, Vedder H, Witt SH, Schulze TG, Rietschel M, Nöthen MM, Cichon S. 2018. Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder. Journal of Affective Disorders. 228:20-25. https://doi.org/10.1016/j.jad.2017.11.068

MLA

Vancouver

Mühleisen TW, Reinbold CS, Forstner AJ, Abramova LI, Alda M, Babadjanova G et al. Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder. Journal of Affective Disorders. 2018 Mar 1;228:20-25. https://doi.org/10.1016/j.jad.2017.11.068

Author

Mühleisen, Thomas W. ; Reinbold, Céline S. ; Forstner, Andreas J. ; Abramova, Lilia I. ; Alda, Martin ; Babadjanova, Gulja ; Bauer, Michael ; Brennan, Paul ; Chuchalin, Alexander ; Cruceanu, Cristiana ; Czerski, Piotr M. ; Degenhardt, Franziska ; Fischer, Sascha B. ; Fullerton, Janice M. ; Gordon, Scott D. ; Grigoroiu-Serbanescu, Maria ; Grof, Paul ; Hauser, Joanna ; Hautzinger, Martin ; Herms, Stefan ; Hoffmann, Per ; Kammerer-Ciernioch, Jutta ; Khusnutdinova, Elza ; Kogevinas, Manolis ; Krasnov, Valery ; Lacour, André ; Laprise, Catherine ; Leber, Markus ; Lissowska, Jolanta ; Lucae, Susanne ; Maaser, Anna ; Maier, Wolfgang ; Martin, Nicholas G. ; Mattheisen, Manuel ; Mayoral, Fermin ; McKay, James D. ; Medland, Sarah E. ; Mitchell, Philip B. ; Moebus, Susanne ; Montgomery, Grant W. ; Müller-Myhsok, Bertram ; Oruc, Lilijana ; Pantelejeva, Galina ; Pfennig, Andrea ; Pojskic, Lejla ; Polonikov, Alexey ; Reif, Andreas ; Rivas, Fabio ; Rouleau, Guy A. ; Schenk, Lorena M. ; Schofield, Peter R. ; Schwarz, Markus ; Streit, Fabian ; Strohmaier, Jana ; Szeszenia-Dabrowska, Neonila ; Tiganov, Alexander S. ; Treutlein, Jens ; Turecki, Gustavo ; Vedder, Helmut ; Witt, Stephanie H. ; Schulze, Thomas G. ; Rietschel, Marcella ; Nöthen, Markus M. ; Cichon, Sven. / Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder. In: Journal of Affective Disorders. 2018 ; Vol. 228. pp. 20-25.

Bibtex

@article{6f342b86fe244c5ca8845522ec0636d0,
title = "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 (P FDR = 0.0377), and NCAM signaling for neurite out-growth, for which 11 out of 62 genes were BD associated (P FDR = 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. ",
keywords = "Bipolar disorder, GRB2 events in ERBB2 signaling, NCAM signaling for neurite out-growth, Neurodevelopmental disorder, Pathway analysis",
author = "M{\"u}hleisen, {Thomas W.} and Reinbold, {C{\'e}line S.} and Forstner, {Andreas J.} and Abramova, {Lilia I.} and Martin Alda and Gulja Babadjanova and Michael Bauer and Paul Brennan and Alexander Chuchalin and Cristiana Cruceanu and Czerski, {Piotr M.} and Franziska Degenhardt and Fischer, {Sascha B.} and Fullerton, {Janice M.} and Gordon, {Scott D.} and Maria Grigoroiu-Serbanescu and Paul Grof and Joanna Hauser and Martin Hautzinger and Stefan Herms and Per Hoffmann and Jutta Kammerer-Ciernioch and Elza Khusnutdinova and Manolis Kogevinas and Valery Krasnov and Andr{\'e} Lacour and Catherine Laprise and Markus Leber and Jolanta Lissowska and Susanne Lucae and Anna Maaser and Wolfgang Maier and Martin, {Nicholas G.} and Manuel Mattheisen and Fermin Mayoral and McKay, {James D.} and Medland, {Sarah E.} and Mitchell, {Philip B.} and Susanne Moebus and Montgomery, {Grant W.} and Bertram M{\"u}ller-Myhsok and Lilijana Oruc and Galina Pantelejeva and Andrea Pfennig and Lejla Pojskic and Alexey Polonikov and Andreas Reif and Fabio Rivas and Rouleau, {Guy A.} and Schenk, {Lorena M.} and Schofield, {Peter R.} and Markus Schwarz and Fabian Streit and Jana Strohmaier and Neonila Szeszenia-Dabrowska and Tiganov, {Alexander S.} and Jens Treutlein and Gustavo Turecki and Helmut Vedder and Witt, {Stephanie H.} and Schulze, {Thomas G.} and Marcella Rietschel and N{\"o}then, {Markus M.} and Sven Cichon",
year = "2018",
month = mar,
day = "1",
doi = "10.1016/j.jad.2017.11.068",
language = "English",
volume = "228",
pages = "20--25",
journal = "Journal of Affective Disorders",
issn = "0165-0327",
publisher = "Elsevier BV",

}

RIS

TY - JOUR

T1 - Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder

AU - Mühleisen, Thomas W.

AU - Reinbold, Céline S.

AU - Forstner, Andreas J.

AU - Abramova, Lilia I.

AU - Alda, Martin

AU - Babadjanova, Gulja

AU - Bauer, Michael

AU - Brennan, Paul

AU - Chuchalin, Alexander

AU - Cruceanu, Cristiana

AU - Czerski, Piotr M.

AU - Degenhardt, Franziska

AU - Fischer, Sascha B.

AU - Fullerton, Janice M.

AU - Gordon, Scott D.

AU - Grigoroiu-Serbanescu, Maria

AU - Grof, Paul

AU - Hauser, Joanna

AU - Hautzinger, Martin

AU - Herms, Stefan

AU - Hoffmann, Per

AU - Kammerer-Ciernioch, Jutta

AU - Khusnutdinova, Elza

AU - Kogevinas, Manolis

AU - Krasnov, Valery

AU - Lacour, André

AU - Laprise, Catherine

AU - Leber, Markus

AU - Lissowska, Jolanta

AU - Lucae, Susanne

AU - Maaser, Anna

AU - Maier, Wolfgang

AU - Martin, Nicholas G.

AU - Mattheisen, Manuel

AU - Mayoral, Fermin

AU - McKay, James D.

AU - Medland, Sarah E.

AU - Mitchell, Philip B.

AU - Moebus, Susanne

AU - Montgomery, Grant W.

AU - Müller-Myhsok, Bertram

AU - Oruc, Lilijana

AU - Pantelejeva, Galina

AU - Pfennig, Andrea

AU - Pojskic, Lejla

AU - Polonikov, Alexey

AU - Reif, Andreas

AU - Rivas, Fabio

AU - Rouleau, Guy A.

AU - Schenk, Lorena M.

AU - Schofield, Peter R.

AU - Schwarz, Markus

AU - Streit, Fabian

AU - Strohmaier, Jana

AU - Szeszenia-Dabrowska, Neonila

AU - Tiganov, Alexander S.

AU - Treutlein, Jens

AU - Turecki, Gustavo

AU - Vedder, Helmut

AU - Witt, Stephanie H.

AU - Schulze, Thomas G.

AU - Rietschel, Marcella

AU - Nöthen, Markus M.

AU - Cichon, Sven

PY - 2018/3/1

Y1 - 2018/3/1

N2 - 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 (P FDR = 0.0377), and NCAM signaling for neurite out-growth, for which 11 out of 62 genes were BD associated (P FDR = 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.

AB - 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 (P FDR = 0.0377), and NCAM signaling for neurite out-growth, for which 11 out of 62 genes were BD associated (P FDR = 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.

KW - Bipolar disorder

KW - GRB2 events in ERBB2 signaling

KW - NCAM signaling for neurite out-growth

KW - Neurodevelopmental disorder

KW - Pathway analysis

UR - http://www.scopus.com/inward/record.url?scp=85036534566&partnerID=8YFLogxK

U2 - 10.1016/j.jad.2017.11.068

DO - 10.1016/j.jad.2017.11.068

M3 - Journal article

C2 - 29197740

AN - SCOPUS:85036534566

VL - 228

SP - 20

EP - 25

JO - Journal of Affective Disorders

JF - Journal of Affective Disorders

SN - 0165-0327

ER -