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@ARTICLE{Forstner:874604,
author = {Forstner, Andreas J and Fischer, Sascha B and Schenk,
Lorena M and Strohmaier, Jana and Maaser-Hecker, Anna and
Reinbold, Céline S and Sivalingam, Sugirthan and Hecker,
Julian and Streit, Fabian and Degenhardt, Franziska and
Witt, Stephanie H and Schumacher, Johannes and Thiele,
Holger and Nürnberg, Peter and Guzman-Parra, José and
Orozco Diaz, Guillermo and Auburger, Georg and Albus, Margot
and Borrmann-Hassenbach, Margitta and González, Maria José
and Gil Flores, Susana and Cabaleiro Fabeiro, Francisco J
and Del Río Noriega, Francisco and Perez Perez, Fermin and
Haro González, Jesus and Rivas, Fabio and Mayoral, Fermin
and Bauer, Michael and Pfennig, Andrea and Reif, Andreas and
Herms, Stefan and Hoffmann, Per and Pirooznia, Mehdi and
Goes, Fernando S and Rietschel, Marcella and Nöthen, Markus
M and Cichon, Sven},
title = {{W}hole-exome sequencing of 81 individuals from 27 multiply
affected bipolar disorder families},
journal = {Translational Psychiatry},
volume = {10},
number = {1},
issn = {2158-3188},
address = {London},
publisher = {Nature Publishing Group},
reportid = {FZJ-2020-01532},
pages = {57},
year = {2020},
abstract = {Bipolar disorder (BD) is a highly heritable
neuropsychiatric disease characterized by recurrent episodes
of depression and mania. Research suggests that the
cumulative impact of common alleles explains $25-38\%$ of
phenotypic variance, and that rare variants may contribute
to BD susceptibility. To identify rare, high-penetrance
susceptibility variants for BD, whole-exome sequencing (WES)
was performed in three affected individuals from each of 27
multiply affected families from Spain and Germany. WES
identified 378 rare, non-synonymous, and potentially
functional variants. These spanned 368 genes, and were
carried by all three affected members in at least one
family. Eight of the 368 genes harbored rare variants that
were implicated in at least two independent families. In an
extended segregation analysis involving additional family
members, five of these eight genes harbored variants showing
full or nearly full cosegregation with BD. These included
the brain-expressed genes RGS12 and NCKAP5, which were
considered the most promising BD candidates on the basis of
independent evidence. Gene enrichment analysis for all 368
genes revealed significant enrichment for four pathways,
including genes reported in de novo studies of autism
(padj < 0.006) and schizophrenia (padj = 0.015).
These results suggest a possible genetic overlap with BD for
autism and schizophrenia at the rare-sequence-variant level.
The present study implicates novel candidate genes for BD
development, and may contribute to an improved understanding
of the biological basis of this common and often devastating
disease.},
cin = {INM-1},
ddc = {610},
cid = {I:(DE-Juel1)INM-1-20090406},
pnm = {571 - Connectivity and Activity (POF3-571)},
pid = {G:(DE-HGF)POF3-571},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32066727},
pmc = {pmc:PMC7026119},
UT = {WOS:000515818400003},
doi = {10.1038/s41398-020-0732-y},
url = {https://juser.fz-juelich.de/record/874604},
}