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

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,...

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Autores principales: Leonenko, Ganna, Di Florio, Arianna, Allardyce, Judith, Forty, Liz, Knott, Sarah, Jones, Lisa, Gordon‐Smith, Katherine, Owen, Michael J., Jones, Ian, Walters, James, Craddock, Nick, O'Donovan, Michael C., Escott‐Price, Valentina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6001555/
https://www.ncbi.nlm.nih.gov/pubmed/29671935
http://dx.doi.org/10.1002/ajmg.b.32635
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author Leonenko, Ganna
Di Florio, Arianna
Allardyce, Judith
Forty, Liz
Knott, Sarah
Jones, Lisa
Gordon‐Smith, Katherine
Owen, Michael J.
Jones, Ian
Walters, James
Craddock, Nick
O'Donovan, Michael C.
Escott‐Price, Valentina
author_facet Leonenko, Ganna
Di Florio, Arianna
Allardyce, Judith
Forty, Liz
Knott, Sarah
Jones, Lisa
Gordon‐Smith, Katherine
Owen, Michael J.
Jones, Ian
Walters, James
Craddock, Nick
O'Donovan, Michael C.
Escott‐Price, Valentina
author_sort Leonenko, Ganna
collection PubMed
description 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.
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spelling pubmed-60015552018-06-21 A data‐driven investigation of relationships between bipolar psychotic symptoms and schizophrenia genome‐wide significant genetic loci Leonenko, Ganna Di Florio, Arianna Allardyce, Judith Forty, Liz Knott, Sarah Jones, Lisa Gordon‐Smith, Katherine Owen, Michael J. Jones, Ian Walters, James Craddock, Nick O'Donovan, Michael C. Escott‐Price, Valentina Am J Med Genet B Neuropsychiatr Genet Research Articles 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. John Wiley and Sons Inc. 2018-04-19 2018-06 /pmc/articles/PMC6001555/ /pubmed/29671935 http://dx.doi.org/10.1002/ajmg.b.32635 Text en © 2018 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Leonenko, Ganna
Di Florio, Arianna
Allardyce, Judith
Forty, Liz
Knott, Sarah
Jones, Lisa
Gordon‐Smith, Katherine
Owen, Michael J.
Jones, Ian
Walters, James
Craddock, Nick
O'Donovan, Michael C.
Escott‐Price, Valentina
A data‐driven investigation of relationships between bipolar psychotic symptoms and schizophrenia genome‐wide significant genetic loci
title A data‐driven investigation of relationships between bipolar psychotic symptoms and schizophrenia genome‐wide significant genetic loci
title_full A data‐driven investigation of relationships between bipolar psychotic symptoms and schizophrenia genome‐wide significant genetic loci
title_fullStr A data‐driven investigation of relationships between bipolar psychotic symptoms and schizophrenia genome‐wide significant genetic loci
title_full_unstemmed A data‐driven investigation of relationships between bipolar psychotic symptoms and schizophrenia genome‐wide significant genetic loci
title_short A data‐driven investigation of relationships between bipolar psychotic symptoms and schizophrenia genome‐wide significant genetic loci
title_sort data‐driven investigation of relationships between bipolar psychotic symptoms and schizophrenia genome‐wide significant genetic loci
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6001555/
https://www.ncbi.nlm.nih.gov/pubmed/29671935
http://dx.doi.org/10.1002/ajmg.b.32635
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