Whole-exome sequencing of 81 individuals from 27 multiply affected bipolar disorder families

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 iden...

Descripción completa

Detalles Bibliográficos
Autores: Forstner, Andreas J., Fischer, Sascha B., Schenk, Lorena M., Strohmaier, Jana, Maaser-Hecker, Anna, Reinbold, Céline S., Sivalingam, Sugirthan, Hecker, Julian, Streit, Fabian, Degenhardt, Franziska, Witt, Stephanie H., Schumacher, Johannes, Thiele, Holger, Nürnberg, Peter, Guzman-Parra, José, Orozco Diaz, Guillermo, Auburger, Georg, Albus, Margot, Borrmann-Hassenbach, Margitta, González, Maria José, Gil Flores, Susana, Cabaleiro Fabeiro, Francisco J., del Río Noriega, Francisco, Perez Perez, Fermin, Haro González, Jesus, Rivas, Fabio, Mayoral, Fermin, Bauer, Michael, Pfennig, Andrea, Reif, Andreas, Herms, Stefan, Hoffmann, Per, Pirooznia, Mehdi, Goes, Fernando S., Rietschel, Marcella, Nöthen, Markus M., Cichon, Sven
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/17998
Acceso en línea:http://hdl.handle.net/20.500.12105/17998
Access Level:acceso abierto
Palabra clave:Whole exome sequencing
Bipolar disorder
Neuropsychiatry
Genetic predisposition to disease
Secuenciación del exoma completo
Trastorno bipolar
Neuropsiquiatría
Predisposición genética a la enfermedad
Exome
Genetic Predisposition to Disease
Humans
Schizophrenia
Bipolar Disorder
Autistic Disorder
Spain
Germany
Penetrance
Brain
Descripción
Sumario: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.

Similares en LA Referencia