OBJECTIVE: Immunopathogenic mechanisms have been implicated in schizophrenia and bipolar disorder, and genome-wide association studies (GWAS) point to the major histocompatibility complex, a region that contains many immune-related genes. One of the strongest candidate risk genes for schizophrenia and bipolar disorder is the NOTCH4 gene within the major histocompatibility complex. The authors investigated the NOTCH4 gene expression in individuals with bipolar disorder and schizophrenia relative to healthy comparison subjects and identified putative expression quantitative trait loci in and around the NOTCH4 gene. METHOD: The authors measured and compared NOTCH4 mRNA in whole blood in 690 individuals (479 patients and 211 healthy comparison subjects) and adjusted for a range of confounders. The authors also genotyped 20 single-nucleotide polymorphisms (SNPs) and investigated possible associations between expression quantitative trait loci and NOTCH4 expression. RESULTS: The authors found a strong association between NOTCH4 expression and bipolar disorder after adjusting for a range of confounders and multiple testing. In addition, seven SNPs within the NOTCH4 gene region were associated with enhanced NOTCH4 mRNA levels. Three of these expression quantitative trait loci were independent (not in linkage disequilibrium). CONCLUSIONS: The results indicate that the association between NOTCH4 DNA markers and bipolar disorder is related to altered function at the mRNA level, supporting the notion that NOTCH4 pathways are involved in the pathophysiology of bipolar disorder.
OBJECTIVE: Immunopathogenic mechanisms have been implicated in schizophrenia and bipolar disorder, and genome-wide association studies (GWAS) point to the major histocompatibility complex, a region that contains many immune-related genes. One of the strongest candidate risk genes for schizophrenia and bipolar disorder is the NOTCH4 gene within the major histocompatibility complex. The authors investigated the NOTCH4 gene expression in individuals with bipolar disorder and schizophrenia relative to healthy comparison subjects and identified putative expression quantitative trait loci in and around the NOTCH4 gene. METHOD: The authors measured and compared NOTCH4 mRNA in whole blood in 690 individuals (479 patients and 211 healthy comparison subjects) and adjusted for a range of confounders. The authors also genotyped 20 single-nucleotide polymorphisms (SNPs) and investigated possible associations between expression quantitative trait loci and NOTCH4 expression. RESULTS: The authors found a strong association between NOTCH4 expression and bipolar disorder after adjusting for a range of confounders and multiple testing. In addition, seven SNPs within the NOTCH4 gene region were associated with enhanced NOTCH4 mRNA levels. Three of these expression quantitative trait loci were independent (not in linkage disequilibrium). CONCLUSIONS: The results indicate that the association between NOTCH4 DNA markers and bipolar disorder is related to altered function at the mRNA level, supporting the notion that NOTCH4 pathways are involved in the pathophysiology of bipolar disorder.
Authors: Eva Zsuzsanna Hoseth; Thor Ueland; Ingrid Dieset; Rebecca Birnbaum; Joo Heon Shin; Joel Edward Kleinman; Thomas Michael Hyde; Ragni Helene Mørch; Sigrun Hope; Tove Lekva; Aurelija Judita Abraityte; Annika E Michelsen; Ingrid Melle; Lars Tjelta Westlye; Torill Ueland; Srdjan Djurovic; Pål Aukrust; Daniel R Weinberger; Ole Andreas Andreassen Journal: Schizophr Bull Date: 2017-07-01 Impact factor: 9.306
Authors: Eva Z Hoseth; Florian Krull; Ingrid Dieset; Ragni H Mørch; Sigrun Hope; Erlend S Gardsjord; Nils Eiel Steen; Ingrid Melle; Hans-Richard Brattbakk; Vidar M Steen; Pål Aukrust; Srdjan Djurovic; Ole A Andreassen; Thor Ueland Journal: Sci Rep Date: 2018-03-28 Impact factor: 4.379
Authors: Eva Z Hoseth; Florian Krull; Ingrid Dieset; Ragni H Mørch; Sigrun Hope; Erlend S Gardsjord; Nils Eiel Steen; Ingrid Melle; Hans-Richard Brattbakk; Vidar M Steen; Pål Aukrust; Srdjan Djurovic; Ole A Andreassen; Thor Ueland Journal: Transl Psychiatry Date: 2018-03-06 Impact factor: 6.222
Authors: Ole A Andreassen; Wesley K Thompson; Andrew J Schork; Stephan Ripke; Morten Mattingsdal; John R Kelsoe; Kenneth S Kendler; Michael C O'Donovan; Dan Rujescu; Thomas Werge; Pamela Sklar; J Cooper Roddey; Chi-Hua Chen; Linda McEvoy; Rahul S Desikan; Srdjan Djurovic; Anders M Dale Journal: PLoS Genet Date: 2013-04-25 Impact factor: 5.917
Authors: J Song; S E Bergen; A Di Florio; R Karlsson; A Charney; D M Ruderfer; E A Stahl; K D Chambert; J L Moran; K Gordon-Smith; L Forty; E K Green; I Jones; L Jones; E M Scolnick; P Sklar; J W Smoller; P Lichtenstein; C Hultman; N Craddock; M Landén; Jordan W Smoller; Roy H Perlis; Phil Hyoun Lee; Victor M Castro; Alison G Hoffnagle; Pamela Sklar; Eli A Stahl; Shaun M Purcell; Douglas M Ruderfer; Alexander W Charney; Panos Roussos; Carlos Pato Michele Pato; Helen Medeiros; Janet Sobel; Nick Craddock; Ian Jones; Liz Forty; Arianna Di Florio; Elaine Green; Lisa Jones; Katherine Gordon-Smith; Mikael Landen; Christina Hultman; Anders Jureus; Sarah Bergen; Steven McCarroll; Jennifer Moran; Jordan W Smoller; Kimberly Chambert; Richard A Belliveau Journal: Mol Psychiatry Date: 2015-10-27 Impact factor: 15.992