Forstner, Andreas J., Fischer, Sascha B., Schenk, Lorena M., Strohmaier, Jana ORCID: 0000-0002-4364-1487, Maaser-Hecker, Anna, Reinbold, Celine S., Sivalingam, Sugirthan ORCID: 0000-0001-5239-5137, Hecker, Julian, Streit, Fabian ORCID: 0000-0003-1080-4339, Degenhardt, Franziska, Witt, Stephanie H., Schumacher, Johannes, Thiele, Holger ORCID: 0000-0002-0169-998X, Nuernberg, Peter, Guzman-Parra, Jose ORCID: 0000-0002-1463-6435, Orozco Diaz, Guillermo, Auburger, Georg, Albus, Margot, Borrmann-Hassenbach, Margitta, Jose Gonzalez, Maria, Gil Flores, Susana, Cabaleiro Fabeiro, Francisco J., del Rio Noriega, Francisco, Perez Perez, Fermin, Haro Gonzalez, Jesus, Rivas, Fabio, Mayoral, Fermin, Bauer, Michael, Pfennig, Andrea, Reif, Andreas, Herms, Stefan, Hoffmann, Per, Pirooznia, Mehdi ORCID: 0000-0002-4210-6458, Goes, Fernando S., Rietschel, Marcella, Noethen, Markus M. and Cichon, Sven (2020). Whole-exome sequencing of 81 individuals from 27 multiply affected bipolar disorder families. Transl. Psychiatr., 10 (1). LONDON: SPRINGERNATURE. ISSN 2158-3188

Full text not available from this repository.

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 (p(adj) < 0.006) and schizophrenia (p(adj) = 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Forstner, Andreas J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fischer, Sascha B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schenk, Lorena M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Strohmaier, JanaUNSPECIFIEDorcid.org/0000-0002-4364-1487UNSPECIFIED
Maaser-Hecker, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reinbold, Celine S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sivalingam, SugirthanUNSPECIFIEDorcid.org/0000-0001-5239-5137UNSPECIFIED
Hecker, JulianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Streit, FabianUNSPECIFIEDorcid.org/0000-0003-1080-4339UNSPECIFIED
Degenhardt, FranziskaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Witt, Stephanie H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schumacher, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thiele, HolgerUNSPECIFIEDorcid.org/0000-0002-0169-998XUNSPECIFIED
Nuernberg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guzman-Parra, JoseUNSPECIFIEDorcid.org/0000-0002-1463-6435UNSPECIFIED
Orozco Diaz, GuillermoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Auburger, GeorgUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Albus, MargotUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borrmann-Hassenbach, MargittaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jose Gonzalez, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gil Flores, SusanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cabaleiro Fabeiro, Francisco J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
del Rio Noriega, FranciscoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perez Perez, FerminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haro Gonzalez, JesusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rivas, FabioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mayoral, FerminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bauer, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfennig, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reif, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herms, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoffmann, PerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pirooznia, MehdiUNSPECIFIEDorcid.org/0000-0002-4210-6458UNSPECIFIED
Goes, Fernando S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rietschel, MarcellaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Noethen, Markus M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cichon, SvenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-345467
DOI: 10.1038/s41398-020-0732-y
Journal or Publication Title: Transl. Psychiatr.
Volume: 10
Number: 1
Date: 2020
Publisher: SPRINGERNATURE
Place of Publication: LONDON
ISSN: 2158-3188
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GENOME-WIDE ASSOCIATION; DE-NOVO MUTATIONS; RARE SUSCEPTIBILITY VARIANTS; SPECTRUM DISORDER; SCHIZOPHRENIA; AUTISM; DATABASE; LOCI; CYTOSKELETON; DISEASESMultiple languages
PsychiatryMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/34546

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item