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Exome sequencing in large, multiplex bipolar disorder families from Cuba
Bipolar disorder (BD) is a major psychiatric illness affecting around 1% of the global population. BD is characterized by recurrent manic and depressive episodes, and has an estimated heritability of around 70%. Research has identified the first BD susceptibility genes. However, the underlying pathw...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209204/ https://www.ncbi.nlm.nih.gov/pubmed/30379966 http://dx.doi.org/10.1371/journal.pone.0205895 |
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author | Maaser, Anna Forstner, Andreas J. Strohmaier, Jana Hecker, Julian Ludwig, Kerstin U. Sivalingam, Sugirthan Streit, Fabian Degenhardt, Franziska Witt, Stephanie H. Reinbold, Céline S. Koller, Anna C. Raff, Ruth Heilmann-Heimbach, Stefanie Fischer, Sascha B. Herms, Stefan Hoffmann, Per Thiele, Holger Nürnberg, Peter Löhlein Fier, Heide Orozco-Díaz, Guillermo Carmenate-Naranjo, Deinys Proenza-Barzaga, Niurka Auburger, Georg W. J. Andlauer, Till F. M. Cichon, Sven Marcheco-Teruel, Beatriz Mors, Ole Rietschel, Marcella Nöthen, Markus M. |
author_facet | Maaser, Anna Forstner, Andreas J. Strohmaier, Jana Hecker, Julian Ludwig, Kerstin U. Sivalingam, Sugirthan Streit, Fabian Degenhardt, Franziska Witt, Stephanie H. Reinbold, Céline S. Koller, Anna C. Raff, Ruth Heilmann-Heimbach, Stefanie Fischer, Sascha B. Herms, Stefan Hoffmann, Per Thiele, Holger Nürnberg, Peter Löhlein Fier, Heide Orozco-Díaz, Guillermo Carmenate-Naranjo, Deinys Proenza-Barzaga, Niurka Auburger, Georg W. J. Andlauer, Till F. M. Cichon, Sven Marcheco-Teruel, Beatriz Mors, Ole Rietschel, Marcella Nöthen, Markus M. |
author_sort | Maaser, Anna |
collection | PubMed |
description | Bipolar disorder (BD) is a major psychiatric illness affecting around 1% of the global population. BD is characterized by recurrent manic and depressive episodes, and has an estimated heritability of around 70%. Research has identified the first BD susceptibility genes. However, the underlying pathways and regulatory networks remain largely unknown. Research suggests that the cumulative impact of common alleles with small effects explains only around 25–38% of the phenotypic variance for BD. A plausible hypothesis therefore is that rare, high penetrance variants may contribute to BD risk. The present study investigated the role of rare, nonsynonymous, and potentially functional variants via whole exome sequencing in 15 BD cases from two large, multiply affected families from Cuba. The high prevalence of BD in these pedigrees renders them promising in terms of the identification of genetic risk variants with large effect sizes. In addition, SNP array data were used to calculate polygenic risk scores for affected and unaffected family members. After correction for multiple testing, no significant increase in polygenic risk scores for common, BD-associated genetic variants was found in BD cases compared to healthy relatives. Exome sequencing identified a total of 17 rare and potentially damaging variants in 17 genes. The identified variants were shared by all investigated BD cases in the respective pedigree. The most promising variant was located in the gene SERPING1 (p.L349F), which has been reported previously as a genome-wide significant risk gene for schizophrenia. The present data suggest novel candidate genes for BD susceptibility, and may facilitate the discovery of disease-relevant pathways and regulatory networks. |
format | Online Article Text |
id | pubmed-6209204 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-62092042018-11-19 Exome sequencing in large, multiplex bipolar disorder families from Cuba Maaser, Anna Forstner, Andreas J. Strohmaier, Jana Hecker, Julian Ludwig, Kerstin U. Sivalingam, Sugirthan Streit, Fabian Degenhardt, Franziska Witt, Stephanie H. Reinbold, Céline S. Koller, Anna C. Raff, Ruth Heilmann-Heimbach, Stefanie Fischer, Sascha B. Herms, Stefan Hoffmann, Per Thiele, Holger Nürnberg, Peter Löhlein Fier, Heide Orozco-Díaz, Guillermo Carmenate-Naranjo, Deinys Proenza-Barzaga, Niurka Auburger, Georg W. J. Andlauer, Till F. M. Cichon, Sven Marcheco-Teruel, Beatriz Mors, Ole Rietschel, Marcella Nöthen, Markus M. PLoS One Research Article Bipolar disorder (BD) is a major psychiatric illness affecting around 1% of the global population. BD is characterized by recurrent manic and depressive episodes, and has an estimated heritability of around 70%. Research has identified the first BD susceptibility genes. However, the underlying pathways and regulatory networks remain largely unknown. Research suggests that the cumulative impact of common alleles with small effects explains only around 25–38% of the phenotypic variance for BD. A plausible hypothesis therefore is that rare, high penetrance variants may contribute to BD risk. The present study investigated the role of rare, nonsynonymous, and potentially functional variants via whole exome sequencing in 15 BD cases from two large, multiply affected families from Cuba. The high prevalence of BD in these pedigrees renders them promising in terms of the identification of genetic risk variants with large effect sizes. In addition, SNP array data were used to calculate polygenic risk scores for affected and unaffected family members. After correction for multiple testing, no significant increase in polygenic risk scores for common, BD-associated genetic variants was found in BD cases compared to healthy relatives. Exome sequencing identified a total of 17 rare and potentially damaging variants in 17 genes. The identified variants were shared by all investigated BD cases in the respective pedigree. The most promising variant was located in the gene SERPING1 (p.L349F), which has been reported previously as a genome-wide significant risk gene for schizophrenia. The present data suggest novel candidate genes for BD susceptibility, and may facilitate the discovery of disease-relevant pathways and regulatory networks. Public Library of Science 2018-10-31 /pmc/articles/PMC6209204/ /pubmed/30379966 http://dx.doi.org/10.1371/journal.pone.0205895 Text en © 2018 Maaser et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Maaser, Anna Forstner, Andreas J. Strohmaier, Jana Hecker, Julian Ludwig, Kerstin U. Sivalingam, Sugirthan Streit, Fabian Degenhardt, Franziska Witt, Stephanie H. Reinbold, Céline S. Koller, Anna C. Raff, Ruth Heilmann-Heimbach, Stefanie Fischer, Sascha B. Herms, Stefan Hoffmann, Per Thiele, Holger Nürnberg, Peter Löhlein Fier, Heide Orozco-Díaz, Guillermo Carmenate-Naranjo, Deinys Proenza-Barzaga, Niurka Auburger, Georg W. J. Andlauer, Till F. M. Cichon, Sven Marcheco-Teruel, Beatriz Mors, Ole Rietschel, Marcella Nöthen, Markus M. Exome sequencing in large, multiplex bipolar disorder families from Cuba |
title | Exome sequencing in large, multiplex bipolar disorder families from Cuba |
title_full | Exome sequencing in large, multiplex bipolar disorder families from Cuba |
title_fullStr | Exome sequencing in large, multiplex bipolar disorder families from Cuba |
title_full_unstemmed | Exome sequencing in large, multiplex bipolar disorder families from Cuba |
title_short | Exome sequencing in large, multiplex bipolar disorder families from Cuba |
title_sort | exome sequencing in large, multiplex bipolar disorder families from cuba |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209204/ https://www.ncbi.nlm.nih.gov/pubmed/30379966 http://dx.doi.org/10.1371/journal.pone.0205895 |
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