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

View/ open
Author
Charney, Alexander
Stahl, Eli
Green, Elaine
Date
2018-12-20Acceptance date
2018-12-12
Type
Article
Publisher
Elsevier
Metadata
Show full item recordAbstract
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.
Journal/conference proceeding
Biological Psychiatry;
Citation
Charney, A.W., Stahl, E., Green, E., Chen, C., Moran, J.L., Chambert, K., Belliveau, R., Forty, L., Gordon-Smith, Katherine , 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 , 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.
Description
Article published in Biological Psychiatry available at https://doi.org/10.1016/j.biopsych.2018.12.009
Collections
Related items
Showing items related by title, author, subject and abstract.
-
Genome‐wide significant locus for Research Diagnostic Criteria Schizoaffective Disorder Bipolar type
Green, Elaine; Di Florio, Arianna; Forty, Liz; Gordon-Smith, Katherine; Grozeva, Detelina; Fraser, Christine; Richards, Alexander L.; Moran, Jennifer L.; Purcell, Shaun; Sklar, Pamela; Kirov, George; Owen, Michael J.; O'Donovan, Michael C.; Craddock, Nick; Jones, Lisa; Jones, Ian R. (Wiley, 2017-08-29)Studies have suggested that Research Diagnostic Criteria for Schizoaffective disorder Bipolar type (RDC-SABP) might identify a more genetically homogenous subgroup of bipolar disorder. Aiming to identify loci associated ... -
Predicting psychological distress of informal carers of individuals with major depression or bipolar disorder
Eden, Samantha (Cardiff Metropolitan University, 2015)Caring for someone with a mental illness is associated with high levels of burden and psychological distress. Understanding the psychological distress of the caring role may be an important factor in preventing the ... -
Predicting psychological distress of informal carers of individuals with major depression or bipolar disorder
Wasley, David; Eden, Samantha (Wiley, 2017-03-19)Caring for someone with a mental illness is associated with high levels of burden and psychological distress. Understanding these factors could be important to prevent the development of physical and mental health problems ...