Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium douglas.ruderfer@vanderbilt.edu, Psychosis Endophenotypes International Consortium, Wellcome Trust Case Control Consortium

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Schizophrenia and bipolar disorder are two distinct diagnoses that share symptomology. Understanding the genetic factors contributing to the shared and disorder-specific symptoms will be crucial for improving diagnosis and treatment. In genetic data consisting of 53,555 cases (20,129 bipolar disorder [BD], 33,426 schizophrenia [SCZ]) and 54,065 controls, we identified 114 genome-wide significant loci implicating synaptic and neuronal pathways shared between disorders. Comparing SCZ to BD (23,585 SCZ, 15,270 BD) identified four genomic regions including one with disorder-independent causal variants and potassium ion response genes as contributing to differences in biology between the disorders. Polygenic risk score (PRS) analyses identified several significant correlations within case-only phenotypes including SCZ PRS with psychotic features and age of onset in BD. For the first time, we discover specific loci that distinguish between BD and SCZ and identify polygenic components underlying multiple symptom dimensions. These results point to the utility of genetics to inform symptomology and potential treatment. Genetic analysis of multiple bipolar disorder and schizophrenia cohorts reveals loci and polygenic risk scores that differentiate the clinical symptoms of these two highly correlated disorders.

Original languageEnglish
Pages (from-to)1705-1715.e16
JournalCell
Volume173
Issue number7
DOIs
Publication statusPublished - 14-06-2018

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Dissection
Bipolar Disorder
Schizophrenia
Genes
Potassium
Ions
Age of Onset
Genome
Phenotype

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium douglas.ruderfer@vanderbilt.edu, Psychosis Endophenotypes International Consortium, & Wellcome Trust Case Control Consortium (2018). Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes. Cell, 173(7), 1705-1715.e16. https://doi.org/10.1016/j.cell.2018.05.046
Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium douglas.ruderfer@vanderbilt.edu ; Psychosis Endophenotypes International Consortium ; Wellcome Trust Case Control Consortium. / Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes. In: Cell. 2018 ; Vol. 173, No. 7. pp. 1705-1715.e16.
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Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium douglas.ruderfer@vanderbilt.edu, Psychosis Endophenotypes International Consortium & Wellcome Trust Case Control Consortium 2018, 'Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes', Cell, vol. 173, no. 7, pp. 1705-1715.e16. https://doi.org/10.1016/j.cell.2018.05.046

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes. / Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium douglas.ruderfer@vanderbilt.edu; Psychosis Endophenotypes International Consortium; Wellcome Trust Case Control Consortium.

In: Cell, Vol. 173, No. 7, 14.06.2018, p. 1705-1715.e16.

Research output: Contribution to journalArticle

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AU - Alexander, Madeline

AU - Alliey-Rodriguez, Ney

AU - Als, Thomas D.

AU - Amin, Farooq

AU - Anjorin, Adebayo

AU - Arranz, Maria J.

AU - Awasthi, Swapnil

AU - Bacanu, Silviu A.

AU - Badner, Judith A.

AU - Baekvad-Hansen, Marie

AU - Bakker, Steven

AU - Band, Gavin

AU - Barchas, Jack D.

AU - Barroso, Ines

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AU - Belliveau, Richard A.

AU - Bellivier, Frank

AU - Bender, Stephan

AU - Bene, Judit

AU - Bergen, Sarah E.

AU - Berrettini, Wade H.

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Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium douglas.ruderfer@vanderbilt.edu, Psychosis Endophenotypes International Consortium, Wellcome Trust Case Control Consortium. Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes. Cell. 2018 Jun 14;173(7):1705-1715.e16. https://doi.org/10.1016/j.cell.2018.05.046