RT Journal Article
T1 Whole-exome sequencing of 81 individuals from 27 multiply affected bipolar disorder families
A1 Forstner, Andreas J.
A1 Fischer, Sascha B.
A1 Schenk, Lorena M.
A1 Strohmaier, Jana
A1 Maaser-Hecker, Anna
A1 Reinbold, Céline S.
A1 Sivalingam, Sugirthan
A1 Hecker, Julian
A1 Streit, Fabian
A1 Degenhardt, Franziska
A1 Witt, Stephanie H.
A1 Schumacher, Johannes
A1 Thiele, Holger
A1 Nürnberg, Peter
A1 Guzman-Parra, José
A1 Orozco Diaz, Guillermo
A1 Auburger, Georg
A1 Albus, Margot
A1 Borrmann-Hassenbach, Margitta
A1 González, Maria José
A1 Gil Flores, Susana
A1 Cabaleiro Fabeiro, Francisco J.
A1 del Río Noriega, Francisco
A1 Perez Perez, Fermin
A1 Haro González, Jesus
A1 Rivas, Fabio
A1 Mayoral, Fermin
A1 Bauer, Michael
A1 Pfennig, Andrea
A1 Reif, Andreas
A1 Herms, Stefan
A1 Hoffmann, Per
A1 Pirooznia, Mehdi
A1 Goes, Fernando S.
A1 Rietschel, Marcella
A1 Nöthen, Markus M.
A1 Cichon, Sven
K1 Whole exome sequencing
K1 Bipolar disorder
K1 Neuropsychiatry
K1 Genetic predisposition to disease
K1 Secuenciación del exoma completo
K1 Trastorno bipolar
K1 Neuropsiquiatría
K1 Predisposición genética a la enfermedad
AB 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.
PB Springer Nature
YR 2020
FD 2020-02-04
LK http://hdl.handle.net/10668/3860
UL http://hdl.handle.net/10668/3860
LA en
NO Forstner AJ, Fischer SB, Schenk LM, Strohmaier J, Maaser-Hecker A, Reinbold CS, et al. Whole-exome sequencing of 81 individuals from 27 multiply affected bipolar disorder families. Transl Psychiatry. 2020 Feb 4;10(1):57
DS RISalud
RD Apr 19, 2025