RT Journal Article
T1 Exome sequencing in large, multiplex bipolar disorder families from Cuba.
A1 Maaser, Anna
A1 Forstner, Andreas J
A1 Strohmaier, Jana
A1 Hecker, Julian
A1 Ludwig, Kerstin U
A1 Sivalingam, Sugirthan
A1 Streit, Fabian
A1 Degenhardt, Franziska
A1 Witt, Stephanie H
A1 Reinbold, Céline S
A1 Koller, Anna C
A1 Raff, Ruth
A1 Heilmann-Heimbach, Stefanie
A1 Fischer, Sascha B
A1 Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, 
A1 Herms, Stefan
A1 Hoffmann, Per
A1 Thiele, Holger
A1 Nürnberg, Peter
A1 Löhlein Fier, Heide
A1 Orozco-Díaz, Guillermo
A1 Carmenate-Naranjo, Deinys
A1 Proenza-Barzaga, Niurka
A1 Auburger, Georg W J
A1 Andlauer, Till F M
A1 Cichon, Sven
A1 Marcheco-Teruel, Beatriz
A1 Mors, Ole
A1 Rietschel, Marcella
A1 Nöthen, Markus M
AB 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.
YR 2018
FD 2018-10-31
LK http://hdl.handle.net/10668/13142
UL http://hdl.handle.net/10668/13142
LA en
DS RISalud
RD Apr 4, 2025