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Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

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  • Douglas M. Ruderfer
  • Stephan Ripke
  • Andrew McQuillin
  • James Boocock
  • Eli A. Stahl
  • Jennifer M.Whitehead Pavlides
  • Niamh Mullins
  • Alexander W. Charney
  • Anil P.S. Ori
  • Loes M.Olde Loohuis
  • Enrico Domenici
  • Arianna Di Florio
  • Sergi Papiol
  • Janos L. Kalman
  • Vassily Trubetskoy
  • Rolf Adolfsson
  • Ingrid Agartz
  • Esben Agerbo
  • Huda Akil
  • Diego Albani
  • Margot Albus
  • Martin Alda
  • Madeline Alexander
  • Ney Alliey-Rodriguez
  • Thomas D. Als
  • Farooq Amin
  • Adebayo Anjorin
  • Maria J. Arranz
  • Swapnil Awasthi
  • Silviu A. Bacanu
  • Judith A. Badner
  • Marie Baekvad-Hansen
  • Steven Bakker
  • Gavin Band
  • Jack D. Barchas
  • Ines Barroso
  • Nicholas Bass
  • Michael Bauer
  • Bernhard T. Baune
  • Martin Begemann
  • Celine Bellenguez
  • Richard A. Belliveau
  • Mark Hansen
  • Thomas Hansen
  • Sandra Meier
  • Merete Nordentoft
  • Line Olsen
  • Tune H. Pers
  • Henrik B. Rasmussen
  • Thomas Werge
  • Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium douglas.ruderfer@vanderbilt.edu
  • Psychosis Endophenotypes International Consortium
  • Wellcome Trust Case-Control Consortium
Vis graf over relationer

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.

OriginalsprogEngelsk
TidsskriftCell
Vol/bind173
Udgave nummer7
Sider (fra-til)1705-1715.e16
ISSN0092-8674
DOI
StatusUdgivet - 14 jun. 2018

ID: 55336700