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

doi: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 [email protected], Psychosis Endophenotypes International Consortium, Wellcome Trust Case-Control Consortium

Institut for Klinisk Medicin

222 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Cell
Vol/bind	173
Udgave nummer	7
Sider (fra-til)	1705-1715.e16
ISSN	0092-8674
DOI	https://doi.org/10.1016/j.cell.2018.05.046
Status	Udgivet - 14 jun. 2018

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10.1016/j.cell.2018.05.046

http://www.cell.com/article/S0092867418306585/pdf

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Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes. / Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium [email protected]; Psychosis Endophenotypes International Consortium; Wellcome Trust Case-Control Consortium.

I: Cell, Bind 173, Nr. 7, 14.06.2018, s. 1705-1715.e16.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium [email protected], Psychosis Endophenotypes International Consortium & Wellcome Trust Case-Control Consortium 2018, 'Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes', Cell, bind 173, nr. 7, s. 1705-1715.e16. https://doi.org/10.1016/j.cell.2018.05.046

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title = "Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes",

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.",

keywords = "bipolar disorder, polygenic risk, psychosis, schizophrenia, subphenotypes",

author = "Ruderfer, {Douglas M.} and Stephan Ripke and Andrew McQuillin and James Boocock and Stahl, {Eli A.} and Pavlides, {Jennifer M.Whitehead} and Niamh Mullins and Charney, {Alexander W.} and Ori, {Anil P.S.} and Loohuis, {Loes M.Olde} and Enrico Domenici and {Di Florio}, Arianna and Sergi Papiol and Kalman, {Janos L.} and Vassily Trubetskoy and Rolf Adolfsson and Ingrid Agartz and Esben Agerbo and Huda Akil and Diego Albani and Margot Albus and Martin Alda and Madeline Alexander and Ney Alliey-Rodriguez and Als, {Thomas D.} and Farooq Amin and Adebayo Anjorin and Arranz, {Maria J.} and Swapnil Awasthi and Bacanu, {Silviu A.} and Badner, {Judith A.} and Marie Baekvad-Hansen and Steven Bakker and Gavin Band and Barchas, {Jack D.} and Ines Barroso and Nicholas Bass and Michael Bauer and Baune, {Bernhard T.} and Pedersen, {Carsten Bocker} and Pedersen, {Marianne Giortz} and Mark Hansen and Thomas Hansen and Tao Li and Merete Nordentoft and Line Olsen and Pers, {Tune H.} and Rasmussen, {Henrik B.} and Hansen, {Christine Soholm} and Thomas Werge and {Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium [email protected]} and {Psychosis Endophenotypes International Consortium} and {Wellcome Trust Case-Control Consortium}",

year = "2018",

month = jun,

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doi = "10.1016/j.cell.2018.05.046",

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AU - Ruderfer, Douglas M.

AU - Ripke, Stephan

AU - McQuillin, Andrew

AU - Boocock, James

AU - Stahl, Eli A.

AU - Pavlides, Jennifer M.Whitehead

AU - Mullins, Niamh

AU - Charney, Alexander W.

AU - Ori, Anil P.S.

AU - Loohuis, Loes M.Olde

AU - Domenici, Enrico

AU - Di Florio, Arianna

AU - Papiol, Sergi

AU - Kalman, Janos L.

AU - Trubetskoy, Vassily

AU - Adolfsson, Rolf

AU - Agartz, Ingrid

AU - Agerbo, Esben

AU - Akil, Huda

AU - Albani, Diego

AU - Albus, Margot

AU - Alda, Martin

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

AU - Bass, Nicholas

AU - Bauer, Michael

AU - Baune, Bernhard T.

AU - Pedersen, Carsten Bocker

AU - Pedersen, Marianne Giortz

AU - Hansen, Mark

AU - Hansen, Thomas

AU - Li, Tao

AU - Nordentoft, Merete

AU - Olsen, Line

AU - Pers, Tune H.

AU - Rasmussen, Henrik B.

AU - Hansen, Christine Soholm

AU - Werge, Thomas

AU - Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium [email protected]

AU - Psychosis Endophenotypes International Consortium

AU - Wellcome Trust Case-Control Consortium

PY - 2018/6/14

Y1 - 2018/6/14

N2 - 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.

AB - 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.

KW - bipolar disorder

KW - polygenic risk

KW - psychosis

KW - schizophrenia

KW - subphenotypes

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U2 - 10.1016/j.cell.2018.05.046

DO - 10.1016/j.cell.2018.05.046

M3 - Journal article

C2 - 29906448

AN - SCOPUS:85048172948

SN - 0092-8674

VL - 173

SP - 1705-1715.e16

JO - Cell

JF - Cell

IS - 7

ER -

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

Abstract

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