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Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

Ruderfer, DM; Ripke, S; McQuillin, A; Boocock, J; Stahl, EA; Pavlides, JMW; Mullins, N; ... Craig, DW; + view all (2018) Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes. Cell , 173 (7) 1705-1715.e16. 10.1016/j.cell.2018.05.046. Green open access

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Abstract

Schizophrenia and bipolar disorder are two distinct diagnoses that share symptomology. Understanding the genetic factors contributing to the shared and disorder-specific symptoms will be crucial for improving diagnosis and treatment. In genetic data consisting of 53,555 cases (20,129 bipolar disorder [BD], 33,426 schizophrenia [SCZ]) and 54,065 controls, we identified 114 genome-wide significant loci implicating synaptic and neuronal pathways shared between disorders. Comparing SCZ to BD (23,585 SCZ, 15,270 BD) identified four genomic regions including one with disorder-independent causal variants and potassium ion response genes as contributing to differences in biology between the disorders. Polygenic risk score (PRS) analyses identified several significant correlations within case-only phenotypes including SCZ PRS with psychotic features and age of onset in BD. For the first time, we discover specific loci that distinguish between BD and SCZ and identify polygenic components underlying multiple symptom dimensions. These results point to the utility of genetics to inform symptomology and potential treatment. Genetic analysis of multiple bipolar disorder and schizophrenia cohorts reveals loci and polygenic risk scores that differentiate the clinical symptoms of these two highly correlated disorders.

Type: Article
Title: Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cell.2018.05.046
Publisher version: https://doi.org/10.1016/j.cell.2018.05.046
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Bipolar disorder, Schizophrenia, subphenotypes, polygenic risk, psychosis
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: http://discovery.ucl.ac.uk/id/eprint/10052955
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