Exome sequencing in large, multiplex bipolar disorder families from Cuba

• Verfasst von: Maaser, Anna [VerfasserIn]
• Verfasst von: Strohmaier, Jana [VerfasserIn]
• Verfasst von: Streit, Fabian [VerfasserIn]
• Verfasst von: Witt, Stephanie [VerfasserIn]
• Verfasst von: Rietschel, Marcella [VerfasserIn]
• Titel: Exome sequencing in large, multiplex bipolar disorder families from Cuba
• Verf.angabe: 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
• E-Jahr: 2018
• Jahr: October 31, 2018
• Umfang: 17 S.
• Fussnoten: Gesehen am 05.08.2019
• Titel Quelle: Enthalten in: PLOS ONE
• Ort Quelle: San Francisco, California, US : PLOS, 2006
• Jahr Quelle: 2018
• Band/Heft Quelle: 13(2018,10) Artikel-Nummer e0205895, Seite 1-17, 17 Seiten
• ISSN Quelle: 1932-6203
• DOI: doi:10.1371/journal.pone.0205895
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Alleles
• Sach-SW: Bipolar disorder
• Sach-SW: Consortia
• Sach-SW: Depression
• Sach-SW: Etiology
• Sach-SW: Genome-wide association studies
• Sach-SW: Molecular genetics
• Sach-SW: Schizophrenia
• K10plus-PPN: 1670544427

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.