Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia

Schizophrenia Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Cross-Disorder Working Group of the Psychiatric Genomics Consortium

Research output: Contribution to journalArticle

160 Citations (Scopus)

Abstract

Bipolar disorder and schizophrenia are two often severe disorders with high heritabilities. Recent studies have demonstrated a large overlap of genetic risk loci between these disorders but diagnostic and molecular distinctions still remain. Here, we perform a combined genome-wide association study (GWAS) of 19 779 bipolar disorder (BP) and schizophrenia (SCZ) cases versus 19 423 controls, in addition to a direct comparison GWAS of 7129 SCZ cases versus 9252 BP cases. In our case-control analysis, we identify five previously identified regions reaching genome-wide significance (CACNA1C, IFI44L, MHC, TRANK1 and MAD1L1) and a novel locus near PIK3C2A. We create a polygenic risk score that is significantly different between BP and SCZ and show a significant correlation between a BP polygenic risk score and the clinical dimension of mania in SCZ patients. Our results indicate that first, combining diseases with similar genetic risk profiles improves power to detect shared risk loci and second, that future direct comparisons of BP and SCZ are likely to identify loci with significant differential effects. Identifying these loci should aid in the fundamental understanding of how these diseases differ biologically. These findings also indicate that combining clinical symptom dimensions and polygenic signatures could provide additional information that may someday be used clinically.

Original languageEnglish
Pages (from-to)1017-1024
Number of pages8
JournalMolecular Psychiatry
Volume19
Issue number9
DOIs
StatePublished - Sep 11 2014

Fingerprint

Bipolar Disorder
Dissection
Schizophrenia
Genome-Wide Association Study
Genetic Loci
Molecular Pathology
Genome

Keywords

  • bipolar
  • clinical symptoms
  • cross disorder
  • polygenic
  • schizophrenia

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Schizophrenia Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, & Cross-Disorder Working Group of the Psychiatric Genomics Consortium (2014). Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia. Molecular Psychiatry, 19(9), 1017-1024. https://doi.org/10.1038/mp.2013.138

Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia. / Schizophrenia Working Group of the Psychiatric Genomics Consortium; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium; Cross-Disorder Working Group of the Psychiatric Genomics Consortium.

In: Molecular Psychiatry, Vol. 19, No. 9, 11.09.2014, p. 1017-1024.

Research output: Contribution to journalArticle

Schizophrenia Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium & Cross-Disorder Working Group of the Psychiatric Genomics Consortium 2014, 'Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia', Molecular Psychiatry, vol. 19, no. 9, pp. 1017-1024. https://doi.org/10.1038/mp.2013.138
Schizophrenia Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Cross-Disorder Working Group of the Psychiatric Genomics Consortium. Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia. Molecular Psychiatry. 2014 Sep 11;19(9):1017-1024. https://doi.org/10.1038/mp.2013.138
Schizophrenia Working Group of the Psychiatric Genomics Consortium ; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium ; Cross-Disorder Working Group of the Psychiatric Genomics Consortium. / Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia. In: Molecular Psychiatry. 2014 ; Vol. 19, No. 9. pp. 1017-1024.
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