University of Worcester Worcester Research and Publications

Contribution of Rare Copy Number Variants to Bipolar Disorder Risk is Limited to Schizoaffective Cases

Charney, A.W., Stahl, E., Green, E., Chen, C., Moran, J.L., Chambert, K., Belliveau, R., Forty, L., Gordon-Smith, Katherine ORCID:, Lee, P., Bromet, E.J., Buckley, P.F., Escamilla, M.A., Fanous, A., Fochtmann, L.J., Lehrer, D.S., Malaspina, D., Marder, S.R., Morley, C.P., Nicolini, H., Perkins, P., Rakofsky, J.J., Rapaport, M.H., Medeiros, H., Sobell, J., Backlund, L., Bergen, S.E., Juréus, A., Schalling, M., Lichtenstein, P., Knowles, J.A., Burdick, K., Jones, I., Jones, Lisa ORCID:, Hultman, C., Perlis, R., Purcell, P., McCarroll, S.A., Pato, C., Pato, M., Di Florio, A., Craddock, N., Landén, M., Smoller, J., Ruderfer, D.M. and Sklar, P. (2019) Contribution of Rare Copy Number Variants to Bipolar Disorder Risk is Limited to Schizoaffective Cases. Biological Psychiatry, 86 (2). pp. 110-119. ISSN Online: 0006-3223

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Background. Genetic risk for bipolar disorder (BD) is conferred through many common alleles, while a role for rare copy number variants (CNVs) is less clear. BD subtypes schizoaffective disorder bipolar type (SAB), bipolar I disorder (BD I) and bipolar II disorder (BD II) differ according to the prominence and timing of psychosis, mania and depression. The factors contributing to the combination of symptoms within a given patient are poorly understood.

Methods. Rare, large CNVs were analyzed in 6353 BD cases (3833 BD I [2676 with psychosis, 850 without psychosis], 1436 BD II, 579 SAB) and 8656 controls. Measures of CNV burden were integrated with polygenic risk scores (PRS) for schizophrenia (SCZ) to evaluate the relative contributions of rare and common variants to psychosis risk.

Results. CNV burden did not differ relative to controls in BD when treated as a single diagnostic entity. Burden in SAB was increased relative to controls (p-value = 0.001), BD I (p-value = 0.0003) and BD II (p-value = 0.0007). Burden and SCZ PRS were increased in SAB compared to BD I with psychosis (CNV p-value = 0.0007, PRS p-value = 0.004) and BD I without psychosis (CNV p-value = 0.0004, PRS p-value = 3.9 x 10-5). Within BD I, psychosis was associated with increased SCZ PRS (p-value = 0.005) but not CNV burden.

Conclusions. CNV burden in BD is limited to SAB. Rare and common genetic variants may contribute differently to risk for psychosis and perhaps other classes of psychiatric symptoms.

Item Type: Article
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Uncontrolled Discrete Keywords: bipolar disorder, copy number variant, genetics, polygenic risk, score, rare variant burden, 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: Katherine Gordon-Smith
Date Deposited: 29 Jul 2019 15:11
Last Modified: 17 Jun 2020 17:31

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