Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Contribution of rare copy number variants to bipolar disorder risk Is limited to schizoaffective cases

Charney, Alexander W., Stahl, Eli A., Green, Elaine K., Chen, Chia-Yen, Moran, Jennifer L., Chambert, Kimberly, Belliveau, Richard A., Forty, Liz, Gordon-Smith, Katherine, Lee, Phil H., Bromet, Evelyn J., Buckley, Peter F., Escamilla, Michael A., Fanous, Ayman H., Fochtmann, Laura J., Lehrer, Douglas S., Malaspina, Dolores, Marder, Stephen R., Morley, Christopher P., Nicolini, Humberto, Perkins, Diana O., Rakofsky, Jeffrey J., Rapaport, Mark H., Medeiros, Helena, Sobell, Janet L., Backlund, Lena, Bergen, Sarah E., Juréus, Anders, Schalling, Martin, Lichtenstein, Paul, Knowles, James A., Burdick, Katherine E., Jones, Ian, Jones, Lisa A., Hultman, Christina M., Perlis, Roy, Purcell, Shaun M., McCarroll, Steven A., Pato, Carlos N., Pato, Michele T., Di Florio, Arianna, Craddock, Nick, Landén, Mikael, Smoller, Jordan W., Ruderfer, Douglas M. and Sklar, Pamela 2019. Contribution of rare copy number variants to bipolar disorder risk Is limited to schizoaffective cases. Biological Psychiatry 86 (2) , pp. 110-119. 10.1016/j.biopsych.2018.12.009
Item availability restricted.

[img] PDF - Accepted Post-Print Version
Restricted to Repository staff only until 20 December 2019 due to copyright restrictions.

Download (272kB)

Abstract

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. Subtypes of BD including 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 genetic factors contributing to the combination of symptoms among these subtypes are poorly understood. Methods Rare large CNVs were analyzed in 6353 BD cases (3833 BD I [2676 with psychosis, 850 without psychosis, and 307 with unknown psychosis history], 1436 BD II, 579 SAB, and 505 BD not otherwise specified) and 8656 controls. CNV burden and a polygenic risk score (PRS) for schizophrenia were used to evaluate the relative contributions of rare and common variants to risk of BD, BD subtypes, and psychosis. Results CNV burden did not differ between BD and controls when treated as a single diagnostic entity. However, burden in SAB was increased relative to controls (p = .001), BD I (p = .0003), and BD II (p = .0007). Burden and schizophrenia PRSs were increased in SAB compared with BD I with psychosis (CNV p = .0007, PRS p = .004), and BD I without psychosis (CNV p = .0004, PRS p = 3.9 × 10−5). Within BD I, psychosis was associated with increased schizophrenia PRSs (p = .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
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Elsevier
ISSN: 0006-3223
Date of First Compliant Deposit: 7 February 2019
Date of Acceptance: 20 December 2019
Last Modified: 18 Oct 2019 13:58
URI: http://orca-mwe.cf.ac.uk/id/eprint/119296

Citation Data

Cited 1 time in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics