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Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

Bipolar Disorder Working Group of the Psychiatric Consortia, and Schizophrenia Working Group of the Psychiatric Consortia, and Gordon-Smith, Katherine and Jones, Lisa (2018) Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes. Cell, 173 (7). pp. 1705-1715. ISSN 0092-8674 Online: 1097-4172

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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.

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Uncontrolled Keywords: bipolar disorder, schizophrenia, subphenotypes, polygenic risk, psychosis
Subjects: B Philosophy. Psychology. Religion > BF Psychology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions: Academic Departments > Institute of Health and Society
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Depositing User: Katherine Gordon-Smith
Date Deposited: 12 Jul 2018 12:10
Last Modified: 27 Jul 2018 08:53
URI: https://eprints.worc.ac.uk/id/eprint/6889

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