RESUMO
Schizophrenia and bipolar disorder are serious mental illnesses that affect more than 2% of adults. While large-scale genetics studies have identified genomic regions associated with disease risk, less is known about the molecular mechanisms by which risk alleles with small effects lead to schizophrenia and bipolar disorder. In order to fill this gap between genetics and disease phenotype, we have undertaken a multi-cohort genomics study of postmortem brains from controls, individuals with schizophrenia and bipolar disorder. Here we present a public resource of functional genomic data from the dorsolateral prefrontal cortex (DLPFC; Brodmann areas 9 and 46) of 986 individuals from 4 separate brain banks, including 353 diagnosed with schizophrenia and 120 with bipolar disorder. The genomic data include RNA-seq and SNP genotypes on 980 individuals, and ATAC-seq on 269 individuals, of which 264 are a subset of individuals with RNA-seq. We have performed extensive preprocessing and quality control on these data so that the research community can take advantage of this public resource available on the Synapse platform at http://CommonMind.org .
Assuntos
Transtorno Bipolar , Esquizofrenia , Transtorno Bipolar/genética , Transtorno Bipolar/patologia , Estudos de Coortes , Epigenômica , Humanos , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/patologia , Esquizofrenia/genética , Esquizofrenia/patologia , TranscriptomaAssuntos
Encéfalo/patologia , Linfadenite Histiocítica Necrosante/patologia , Meningite Asséptica/patologia , Abdome/patologia , Diagnóstico Diferencial , Feminino , Linfadenite Histiocítica Necrosante/diagnóstico , Humanos , Linfonodos/patologia , Meningite Asséptica/diagnóstico , Pessoa de Meia-IdadeRESUMO
Hemolytic-uremic syndrome (HUS) is characterized by acute kidney injury with hemolytic anemia and thrombocytopenia. It has diverse etiologies, clinical manifestations, and risk factors. Acute pancreatitis as a cause of HUS is rare in adults. We report a case of 32-year-old male who presented with ethanol-induced acute pancreatitis complicated with hemolytic-uremic syndrome managed with hemodialysis and plasmapheresis.
RESUMO
Over 100 genetic loci harbor schizophrenia-associated variants, yet how these variants confer liability is uncertain. The CommonMind Consortium sequenced RNA from dorsolateral prefrontal cortex of people with schizophrenia (N = 258) and control subjects (N = 279), creating a resource of gene expression and its genetic regulation. Using this resource, â¼20% of schizophrenia loci have variants that could contribute to altered gene expression and liability. In five loci, only a single gene was involved: FURIN, TSNARE1, CNTN4, CLCN3 or SNAP91. Altering expression of FURIN, TSNARE1 or CNTN4 changed neurodevelopment in zebrafish; knockdown of FURIN in human neural progenitor cells yielded abnormal migration. Of 693 genes showing significant case-versus-control differential expression, their fold changes were ≤ 1.33, and an independent cohort yielded similar results. Gene co-expression implicates a network relevant for schizophrenia. Our findings show that schizophrenia is polygenic and highlight the utility of this resource for mechanistic interpretations of genetic liability for brain diseases.