University of Worcester Worcester Research and Publications

A Data-driven Investigation of Relationships Between Bipolar Psychotic Symptoms and Schizophrenia Genome-wide Significant Genetic Loci

Leonenko, G., Di Florio, A., Allardyce, J., Forty, L., Knott, Sarah, Jones, Lisa ORCID:, Gordon-Smith, Katherine ORCID:, Owen, M.J., Jones, I., Walters, J., Craddock, N., O'Donovan, M.C. and Escott-Price, V. (2018) A Data-driven Investigation of Relationships Between Bipolar Psychotic Symptoms and Schizophrenia Genome-wide Significant Genetic Loci. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 177 (4). pp. 468-475. ISSN Online: 1552-485X

Leonenko_et_al-2017-American_Journal_of_Medical_Genetics_Part_B%3A_Neuropsychiatric_Genetics.pdf - Published Version
Available under License Creative Commons Attribution.

Download (458kB) | Preview


The etiologies of bipolar disorder (BD) and schizophrenia include a large number of common risk alleles, many of which are shared across the disorders. BD is clinically heterogeneous and it has been postulated that the pattern of symptoms is in part determined by the particular risk alleles carried, and in particular, that risk alleles also confer liability to schizophrenia influence psychotic symptoms in those with BD. To investigate links between psychotic symptoms in BD and schizophrenia risk alleles we employed a data-driven approach in a genotyped and deeply phenotyped sample of subjects with BD. We used sparse canonical correlation analysis (sCCA) (Witten, Tibshirani, & Hastie, ) to analyze 30 psychotic symptoms, assessed with the OPerational CRITeria checklist, and 82 independent genome-wide significant single nucleotide polymorphisms (SNPs) identified by the Schizophrenia Working group of the Psychiatric Genomics Consortium for which we had data in our BD sample (3,903 subjects). As a secondary analysis, we applied sCCA to larger groups of SNPs, and also to groups of symptoms defined according to a published factor analyses of schizophrenia. sCCA analysis based on individual psychotic symptoms revealed a significant association (p = .033), with the largest weights attributed to a variant on chromosome 3 (rs11411529), chr3:180594593, build 37) and delusions of influence, bizarre behavior and grandiose delusions. sCCA analysis using the same set of SNPs supported association with the same SNP and the group of symptoms defined "factor 3" (p = .012). A significant association was also observed to the "factor 3" phenotype group when we included a greater number of SNPs that were less stringently associated with schizophrenia; although other SNPs contributed to the significant multivariate association result, the greatest weight remained assigned to rs11411529. Our results suggest that the canonical correlation is a useful tool to explore phenotype-genotype relationships. To the best of our knowledge, this is the first study to apply this approach to complex, polygenic psychiatric traits. The sparse canonical correlation approach offers the potential to include a larger number of fine-grained systematic descriptors, and to include genetic markers associated with other disorders that are genetically correlated with BD.

Item Type: Article
Additional Information:

The full-text can be accessed via the Official URL.

Uncontrolled Discrete Keywords: OPCRIT, bipolar, psychosis, schizophrenia, sparse canonical correlation analysis
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
Copyright Info: Open Access
SWORD Depositor: Prof. Pub Router
Depositing User: Katherine Gordon-Smith
Date Deposited: 21 May 2018 15:21
Last Modified: 12 Aug 2020 09:56

Actions (login required)

View Item View Item
Worcester Research and Publications is powered by EPrints 3 which is developed by the School of Electronics and Computer Science at the University of Southampton. More information and software credits.