University of Worcester Worcester Research and Publications

Polygenic Dissection of Diagnosis and Clinical Dimensions of Bipolar Disorder and Schizophrenia

Ruderfer, D.M., Fanous, A.H., Ripke, S., McQuillin, A., Amdur, R.L., Schizophrenia Working Group, of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group, of the Psychiatric Genomics Consortium, Cross-Disorder Working Group, of the Psychiatric Genomics Consortium, Gejman, P.V., O'Donovan, M.C., Andreassen, O.A., Djurovic, S., Hultman, C.M., Kelsoe, J.R., Jamain, S., Landén, M., Leboyer, M., Nimgaonkar, V., Nurnberger, J., Smoller, J.W., Craddock, N., Corvin, A., Sullivan, P.F., Holmans, P., Sklar, P., Kendler, K.S., Gordon-Smith, Katherine ORCID: and Jones, Lisa ORCID: (2014) Polygenic Dissection of Diagnosis and Clinical Dimensions of Bipolar Disorder and Schizophrenia. Molecular Psychiatry, 19. pp. 1017-1024. ISSN Print: 1359-4184 Online: 1476-5578

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Bipolar disorder and schizophrenia are two often severe disorders with high heritabilities. Recent studies have demonstrated a large overlap of genetic risk loci between these disorders but diagnostic and molecular distinctions still remain. Here, we perform a combined genome-wide association study (GWAS) of 19 779 bipolar disorder (BP) and schizophrenia (SCZ) cases versus 19 423 controls, in addition to a direct comparison GWAS of 7129 SCZ cases versus 9252 BP cases. In our case–control analysis, we identify five previously identified regions reaching genome-wide significance (CACNA1C, IFI44L, MHC, TRANK1 and MAD1L1) and a novel locus near PIK3C2A. We create a polygenic risk score that is significantly different between BP and SCZ and show a significant correlation between a BP polygenic risk score and the clinical dimension of mania in SCZ patients. Our results indicate that first, combining diseases with similar genetic risk profiles improves power to detect shared risk loci and second, that future direct comparisons of BP and SCZ are likely to identify loci with significant differential effects. Identifying these loci should aid in the fundamental understanding of how these diseases differ biologically. These findings also indicate that combining clinical symptom dimensions and polygenic signatures could provide additional information that may someday be used clinically.

Item Type: Article
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Uncontrolled Discrete Keywords: bipolar, clinical symptoms, cross disorder, polygenic, schizophrenia
Subjects: B Philosophy. Psychology. Religion > BF Psychology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions: College of Health, Life and Environmental Sciences > School of Allied Health and Community
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Depositing User: Lisa Jones
Date Deposited: 16 Jan 2017 11:06
Last Modified: 17 Jun 2020 17:15

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