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...
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Autor*in:	Anna Maaser [verfasserIn] Andreas J Forstner [verfasserIn] Jana Strohmaier [verfasserIn] Julian Hecker [verfasserIn] Kerstin U Ludwig [verfasserIn] Sugirthan Sivalingam [verfasserIn] Fabian Streit [verfasserIn] Franziska Degenhardt [verfasserIn] Stephanie H Witt [verfasserIn] Céline S Reinbold [verfasserIn] Anna C Koller [verfasserIn] Ruth Raff [verfasserIn] Stefanie Heilmann-Heimbach [verfasserIn] Sascha B Fischer [verfasserIn] Bipolar Disorder Working Group of the Psychiatric Genomics Consortium [verfasserIn] Stefan Herms [verfasserIn] Per Hoffmann [verfasserIn] Holger Thiele [verfasserIn] Peter Nürnberg [verfasserIn] Heide Löhlein Fier [verfasserIn] Guillermo Orozco-Díaz [verfasserIn] Deinys Carmenate-Naranjo [verfasserIn] Niurka Proenza-Barzaga [verfasserIn] Georg W J Auburger [verfasserIn] Till F M Andlauer [verfasserIn] Sven Cichon [verfasserIn] Beatriz Marcheco-Teruel [verfasserIn] Ole Mors [verfasserIn] Marcella Rietschel [verfasserIn] Markus M Nöthen [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2018

Übergeordnetes Werk:	In: PLoS ONE - Public Library of Science (PLoS), 2007, 13(2018), 10, p e0205895
Übergeordnetes Werk:	volume:13 ; year:2018 ; number:10, p e0205895

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1371/journal.pone.0205895

Katalog-ID:	DOAJ004418239

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520			\|a 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.
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700	0		\|a Fabian Streit \|e verfasserin \|4 aut
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700	0		\|a Stephanie H Witt \|e verfasserin \|4 aut
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700	0		\|a Anna C Koller \|e verfasserin \|4 aut
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700	0		\|a Deinys Carmenate-Naranjo \|e verfasserin \|4 aut
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700	0		\|a Till F M Andlauer \|e verfasserin \|4 aut
700	0		\|a Sven Cichon \|e verfasserin \|4 aut
700	0		\|a Beatriz Marcheco-Teruel \|e verfasserin \|4 aut
700	0		\|a Ole Mors \|e verfasserin \|4 aut
700	0		\|a Marcella Rietschel \|e verfasserin \|4 aut
700	0		\|a Markus M Nöthen \|e verfasserin \|4 aut
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allfields	10.1371/journal.pone.0205895 doi (DE-627)DOAJ004418239 (DE-599)DOAJ1678c4857613409997aaacae174fa23f DE-627 ger DE-627 rakwb eng Anna Maaser verfasserin aut Exome sequencing in large, multiplex bipolar disorder families from Cuba. 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Science Q Andreas J Forstner verfasserin aut Jana Strohmaier verfasserin aut Julian Hecker verfasserin aut Kerstin U Ludwig verfasserin aut Sugirthan Sivalingam verfasserin aut Fabian Streit verfasserin aut Franziska Degenhardt verfasserin aut Stephanie H Witt verfasserin aut Céline S Reinbold verfasserin aut Anna C Koller verfasserin aut Ruth Raff verfasserin aut Stefanie Heilmann-Heimbach verfasserin aut Sascha B Fischer verfasserin aut Bipolar Disorder Working Group of the Psychiatric Genomics Consortium verfasserin aut Stefan Herms verfasserin aut Per Hoffmann verfasserin aut Holger Thiele verfasserin aut Peter Nürnberg verfasserin aut Heide Löhlein Fier verfasserin aut Guillermo Orozco-Díaz verfasserin aut Deinys Carmenate-Naranjo verfasserin aut Niurka Proenza-Barzaga verfasserin aut Georg W J Auburger verfasserin aut Till F M Andlauer verfasserin aut Sven Cichon verfasserin aut Beatriz Marcheco-Teruel verfasserin aut Ole Mors verfasserin aut Marcella Rietschel verfasserin aut Markus M Nöthen verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 13(2018), 10, p e0205895 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:13 year:2018 number:10, p e0205895 https://doi.org/10.1371/journal.pone.0205895 kostenfrei https://doaj.org/article/1678c4857613409997aaacae174fa23f kostenfrei http://europepmc.org/articles/PMC6209204?pdf=render kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 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_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2018 10, p e0205895
spelling	10.1371/journal.pone.0205895 doi (DE-627)DOAJ004418239 (DE-599)DOAJ1678c4857613409997aaacae174fa23f DE-627 ger DE-627 rakwb eng Anna Maaser verfasserin aut Exome sequencing in large, multiplex bipolar disorder families from Cuba. 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Science Q Andreas J Forstner verfasserin aut Jana Strohmaier verfasserin aut Julian Hecker verfasserin aut Kerstin U Ludwig verfasserin aut Sugirthan Sivalingam verfasserin aut Fabian Streit verfasserin aut Franziska Degenhardt verfasserin aut Stephanie H Witt verfasserin aut Céline S Reinbold verfasserin aut Anna C Koller verfasserin aut Ruth Raff verfasserin aut Stefanie Heilmann-Heimbach verfasserin aut Sascha B Fischer verfasserin aut Bipolar Disorder Working Group of the Psychiatric Genomics Consortium verfasserin aut Stefan Herms verfasserin aut Per Hoffmann verfasserin aut Holger Thiele verfasserin aut Peter Nürnberg verfasserin aut Heide Löhlein Fier verfasserin aut Guillermo Orozco-Díaz verfasserin aut Deinys Carmenate-Naranjo verfasserin aut Niurka Proenza-Barzaga verfasserin aut Georg W J Auburger verfasserin aut Till F M Andlauer verfasserin aut Sven Cichon verfasserin aut Beatriz Marcheco-Teruel verfasserin aut Ole Mors verfasserin aut Marcella Rietschel verfasserin aut Markus M Nöthen verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 13(2018), 10, p e0205895 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:13 year:2018 number:10, p e0205895 https://doi.org/10.1371/journal.pone.0205895 kostenfrei https://doaj.org/article/1678c4857613409997aaacae174fa23f kostenfrei http://europepmc.org/articles/PMC6209204?pdf=render kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 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_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2018 10, p e0205895
allfields_unstemmed	10.1371/journal.pone.0205895 doi (DE-627)DOAJ004418239 (DE-599)DOAJ1678c4857613409997aaacae174fa23f DE-627 ger DE-627 rakwb eng Anna Maaser verfasserin aut Exome sequencing in large, multiplex bipolar disorder families from Cuba. 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Science Q Andreas J Forstner verfasserin aut Jana Strohmaier verfasserin aut Julian Hecker verfasserin aut Kerstin U Ludwig verfasserin aut Sugirthan Sivalingam verfasserin aut Fabian Streit verfasserin aut Franziska Degenhardt verfasserin aut Stephanie H Witt verfasserin aut Céline S Reinbold verfasserin aut Anna C Koller verfasserin aut Ruth Raff verfasserin aut Stefanie Heilmann-Heimbach verfasserin aut Sascha B Fischer verfasserin aut Bipolar Disorder Working Group of the Psychiatric Genomics Consortium verfasserin aut Stefan Herms verfasserin aut Per Hoffmann verfasserin aut Holger Thiele verfasserin aut Peter Nürnberg verfasserin aut Heide Löhlein Fier verfasserin aut Guillermo Orozco-Díaz verfasserin aut Deinys Carmenate-Naranjo verfasserin aut Niurka Proenza-Barzaga verfasserin aut Georg W J Auburger verfasserin aut Till F M Andlauer verfasserin aut Sven Cichon verfasserin aut Beatriz Marcheco-Teruel verfasserin aut Ole Mors verfasserin aut Marcella Rietschel verfasserin aut Markus M Nöthen verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 13(2018), 10, p e0205895 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:13 year:2018 number:10, p e0205895 https://doi.org/10.1371/journal.pone.0205895 kostenfrei https://doaj.org/article/1678c4857613409997aaacae174fa23f kostenfrei http://europepmc.org/articles/PMC6209204?pdf=render kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 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_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2018 10, p e0205895
allfieldsGer	10.1371/journal.pone.0205895 doi (DE-627)DOAJ004418239 (DE-599)DOAJ1678c4857613409997aaacae174fa23f DE-627 ger DE-627 rakwb eng Anna Maaser verfasserin aut Exome sequencing in large, multiplex bipolar disorder families from Cuba. 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Science Q Andreas J Forstner verfasserin aut Jana Strohmaier verfasserin aut Julian Hecker verfasserin aut Kerstin U Ludwig verfasserin aut Sugirthan Sivalingam verfasserin aut Fabian Streit verfasserin aut Franziska Degenhardt verfasserin aut Stephanie H Witt verfasserin aut Céline S Reinbold verfasserin aut Anna C Koller verfasserin aut Ruth Raff verfasserin aut Stefanie Heilmann-Heimbach verfasserin aut Sascha B Fischer verfasserin aut Bipolar Disorder Working Group of the Psychiatric Genomics Consortium verfasserin aut Stefan Herms verfasserin aut Per Hoffmann verfasserin aut Holger Thiele verfasserin aut Peter Nürnberg verfasserin aut Heide Löhlein Fier verfasserin aut Guillermo Orozco-Díaz verfasserin aut Deinys Carmenate-Naranjo verfasserin aut Niurka Proenza-Barzaga verfasserin aut Georg W J Auburger verfasserin aut Till F M Andlauer verfasserin aut Sven Cichon verfasserin aut Beatriz Marcheco-Teruel verfasserin aut Ole Mors verfasserin aut Marcella Rietschel verfasserin aut Markus M Nöthen verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 13(2018), 10, p e0205895 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:13 year:2018 number:10, p e0205895 https://doi.org/10.1371/journal.pone.0205895 kostenfrei https://doaj.org/article/1678c4857613409997aaacae174fa23f kostenfrei http://europepmc.org/articles/PMC6209204?pdf=render kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 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_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2018 10, p e0205895
allfieldsSound	10.1371/journal.pone.0205895 doi (DE-627)DOAJ004418239 (DE-599)DOAJ1678c4857613409997aaacae174fa23f DE-627 ger DE-627 rakwb eng Anna Maaser verfasserin aut Exome sequencing in large, multiplex bipolar disorder families from Cuba. 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Science Q Andreas J Forstner verfasserin aut Jana Strohmaier verfasserin aut Julian Hecker verfasserin aut Kerstin U Ludwig verfasserin aut Sugirthan Sivalingam verfasserin aut Fabian Streit verfasserin aut Franziska Degenhardt verfasserin aut Stephanie H Witt verfasserin aut Céline S Reinbold verfasserin aut Anna C Koller verfasserin aut Ruth Raff verfasserin aut Stefanie Heilmann-Heimbach verfasserin aut Sascha B Fischer verfasserin aut Bipolar Disorder Working Group of the Psychiatric Genomics Consortium verfasserin aut Stefan Herms verfasserin aut Per Hoffmann verfasserin aut Holger Thiele verfasserin aut Peter Nürnberg verfasserin aut Heide Löhlein Fier verfasserin aut Guillermo Orozco-Díaz verfasserin aut Deinys Carmenate-Naranjo verfasserin aut Niurka Proenza-Barzaga verfasserin aut Georg W J Auburger verfasserin aut Till F M Andlauer verfasserin aut Sven Cichon verfasserin aut Beatriz Marcheco-Teruel verfasserin aut Ole Mors verfasserin aut Marcella Rietschel verfasserin aut Markus M Nöthen verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 13(2018), 10, p e0205895 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:13 year:2018 number:10, p e0205895 https://doi.org/10.1371/journal.pone.0205895 kostenfrei https://doaj.org/article/1678c4857613409997aaacae174fa23f kostenfrei http://europepmc.org/articles/PMC6209204?pdf=render kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 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_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2018 10, p e0205895
language	English
source	In PLoS ONE 13(2018), 10, p e0205895 volume:13 year:2018 number:10, p e0205895
sourceStr	In PLoS ONE 13(2018), 10, p e0205895 volume:13 year:2018 number:10, p e0205895
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Medicine R Science Q
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container_title	PLoS ONE
authorswithroles_txt_mv	Anna Maaser @@aut@@ Andreas J Forstner @@aut@@ Jana Strohmaier @@aut@@ Julian Hecker @@aut@@ Kerstin U Ludwig @@aut@@ Sugirthan Sivalingam @@aut@@ Fabian Streit @@aut@@ Franziska Degenhardt @@aut@@ Stephanie H Witt @@aut@@ Céline S Reinbold @@aut@@ Anna C Koller @@aut@@ Ruth Raff @@aut@@ Stefanie Heilmann-Heimbach @@aut@@ Sascha B Fischer @@aut@@ Bipolar Disorder Working Group of the Psychiatric Genomics Consortium @@aut@@ Stefan Herms @@aut@@ Per Hoffmann @@aut@@ Holger Thiele @@aut@@ Peter Nürnberg @@aut@@ Heide Löhlein Fier @@aut@@ Guillermo Orozco-Díaz @@aut@@ Deinys Carmenate-Naranjo @@aut@@ Niurka Proenza-Barzaga @@aut@@ Georg W J Auburger @@aut@@ Till F M Andlauer @@aut@@ Sven Cichon @@aut@@ Beatriz Marcheco-Teruel @@aut@@ Ole Mors @@aut@@ Marcella Rietschel @@aut@@ Markus M Nöthen @@aut@@
publishDateDaySort_date	2018-01-01T00:00:00Z
hierarchy_top_id	523574592
id	DOAJ004418239
language_de	englisch
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author	Anna Maaser
spellingShingle	Anna Maaser misc Medicine misc R misc Science misc Q Exome sequencing in large, multiplex bipolar disorder families from Cuba.
authorStr	Anna Maaser
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topic_title	Exome sequencing in large, multiplex bipolar disorder families from Cuba
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title	Exome sequencing in large, multiplex bipolar disorder families from Cuba.
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title_full	Exome sequencing in large, multiplex bipolar disorder families from Cuba
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author_browse	Anna Maaser Andreas J Forstner Jana Strohmaier Julian Hecker Kerstin U Ludwig Sugirthan Sivalingam Fabian Streit Franziska Degenhardt Stephanie H Witt Céline S Reinbold Anna C Koller Ruth Raff Stefanie Heilmann-Heimbach Sascha B Fischer Bipolar Disorder Working Group of the Psychiatric Genomics Consortium Stefan Herms Per Hoffmann Holger Thiele Peter Nürnberg Heide Löhlein Fier Guillermo Orozco-Díaz Deinys Carmenate-Naranjo Niurka Proenza-Barzaga Georg W J Auburger Till F M Andlauer Sven Cichon Beatriz Marcheco-Teruel Ole Mors Marcella Rietschel Markus M Nöthen
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title_sort	exome sequencing in large, multiplex bipolar disorder families from cuba
title_auth	Exome sequencing in large, multiplex bipolar disorder families from Cuba.
abstract	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.
abstractGer	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.
abstract_unstemmed	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.
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title_short	Exome sequencing in large, multiplex bipolar disorder families from Cuba.
url	https://doi.org/10.1371/journal.pone.0205895 https://doaj.org/article/1678c4857613409997aaacae174fa23f http://europepmc.org/articles/PMC6209204?pdf=render https://doaj.org/toc/1932-6203
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doi_str	10.1371/journal.pone.0205895
up_date	2024-07-03T23:37:35.118Z
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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. 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Exome sequencing in large, multiplex bipolar disorder families from Cuba.

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