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

A data-driven investigation of relationships between bipolar psychotic symptoms and schizophrenia genome-wide significant genetic loci

Leonenko, Ganna ORCID:, Di Florio, Arianna ORCID:, Allardyce, Judith ORCID:, Forty, Liz, Knott, Sarah, Jones, Lisa ORCID:, Gordon-Smith, Katherine, Owen, Michael J. ORCID:, Jones, Ian ORCID:, Walters, James ORCID:, Craddock, Nick ORCID:, O'Donovan, Michael C. ORCID: and Escott-Price, Valentina ORCID: 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. 10.1002/ajmg.b.32635

[thumbnail of Leonenko_et_al-2017-American_Journal_of_Medical_Genetics_Part_B__Neuropsychiatric_Genetics.pdf]
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, 2009) 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
Date Type: Publication
Status: Published
Schools: Medicine
Advanced Research Computing @ Cardiff (ARCCA)
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Wiley
ISSN: 1552-4841
Date of First Compliant Deposit: 2 May 2018
Date of Acceptance: 27 March 2018
Last Modified: 22 Oct 2023 10:39

Citation Data

Cited 9 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item


Downloads per month over past year

View more statistics