TY  - JOUR
A1  - Maaser, Anna
A1  - Forstner, Andreas Josef
A1  - Strohmaier, Jana
A1  - Hecker, Julian
A1  - Ludwig, Kerstin Urte
A1  - Sivalingam, Sugirthan
A1  - Streit, Fabian
A1  - Degenhardt, Franziska
A1  - Witt, Stephanie
A1  - Reinbold, Céline S.
A1  - Koller, Anna C.
A1  - Raff, Ruth
A1  - Heilmann-Heimbach, Stefanie
A1  - Fischer, Sascha B.
A1  - Herms, Stefan
A1  - Hoffmann, Per
A1  - Thiele, Holger
A1  - Nürnberg, Peter
A1  - Fier, Heide
A1  - Orozco-Díaz, Guillermo
A1  - Carmenate-Naranjo, Deinys
A1  - Proenza-Barzaga, Niurka
A1  - Auburger, Georg
A1  - Andlauer, Till
A1  - Cichon, Sven
A1  - Marcheco-Teruel, Beatriz
A1  - Mors, Ole
A1  - Rietschel, Marcella
A1  - Nöthen, Markus Maria
T1  - Exome sequencing in large, multiplex bipolar disorder families from Cuba
T2  - PLoS one
N2  - 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.
KW  - Bipolar disorder
KW  - Depression
KW  - Genome-wide association studies
KW  - Alleles
KW  - Molecular genetics
KW  - Schizophrenia
KW  - Consortia
KW  - Etiology
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/47471
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-474717
SN  - 1932-6203
N1  - Copyright: © 2018 Maaser et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 13
IS  - (10): e0205895
SP  - 1
EP  - 17
PB  - PLoS
CY  - Lawrence, Kan.
ER  -