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Use of schizophrenia and bipolar disorder polygenic risk scores to identify psychotic disorders

  • Maria Stella Calafato (a1), Johan H. Thygesen (a1), Siri Ranlund (a1), Eirini Zartaloudi (a2), Wiepke Cahn (a3), Benedicto Crespo-Facorro (a4), Álvaro Díez-Revuelta (a5), Marta Di Forti (a6), Genetic Risk and Outcome of Psychosis (GROUP) consortium (a1) (a1) (a1) (a2) (a3) (a4) (a5) (a6) (a7) (a6) (a8) (a3) (a9) (a6) (a10) (a11) (a12) (a1) (a13) (a14) (a15) (a16) (a17) (a13) (a18) (a13) (a13) (a13) (a19), Mei-Hua Hall (a7), Conrad Iyegbe (a6), Assen Jablensky (a8), Rene Kahn (a3), Luba Kalaydjieva (a9), Eugenia Kravariti (a6), Kuang Lin (a10), Colm McDonald (a11), Andrew M. McIntosh (a12), Andrew McQuillin (a1), Psychosis Endophenotypes International Consortium (PEIC) (a1) (a1) (a1) (a2) (a3) (a4) (a5) (a6) (a7) (a6) (a8) (a3) (a9) (a6) (a10) (a11) (a12) (a1) (a13) (a14) (a15) (a16) (a17) (a13) (a18) (a13) (a13) (a13) (a19), Marco Picchioni (a13), Dan Rujescu (a14), Madiha Shaikh (a15), Timothea Toulopoulou (a16), Jim Van Os (a17), Evangelos Vassos (a13), Muriel Walshe (a18), John Powell (a13), Cathryn M. Lewis (a13), Robin M. Murray (a13), Elvira Bramon (a19) and Wellcome Trust Case Control Consortium 2 (WTCCC2) (a1) (a1) (a1) (a2) (a3) (a4) (a5) (a6) (a7) (a6) (a8) (a3) (a9) (a6) (a10) (a11) (a12) (a1) (a13) (a14) (a15) (a16) (a17) (a13) (a18) (a13) (a13) (a13) (a19)...
Abstract
Background

There is increasing evidence for shared genetic susceptibility between schizophrenia and bipolar disorder. Although genetic variants only convey subtle increases in risk individually, their combination into a polygenic risk score constitutes a strong disease predictor.

Aims

To investigate whether schizophrenia and bipolar disorder polygenic risk scores can distinguish people with broadly defined psychosis and their unaffected relatives from controls.

Method

Using the latest Psychiatric Genomics Consortium data, we calculated schizophrenia and bipolar disorder polygenic risk scores for 1168 people with psychosis, 552 unaffected relatives and 1472 controls.

Results

Patients with broadly defined psychosis had dramatic increases in schizophrenia and bipolar polygenic risk scores, as did their relatives, albeit to a lesser degree. However, the accuracy of predictive models was modest.

Conclusions

Although polygenic risk scores are not ready for clinical use, it is hoped that as they are refined they could help towards risk reduction advice and early interventions for psychosis.

Declaration of interest

R.M.M. has received honoraria for lectures from Janssen, Lundbeck, Lilly, Otsuka and Sunovian.

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Copyright
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Corresponding author
Correspondence: Maria Stella Calafato, Mental Health Neuroscience Research Department, Division of Psychiatry, University College London, 149 Tottenham Court Rd, London W1T 7NF, UK. Email: m.calafato@ucl.ac.uk
Footnotes
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*

Authors who are members of the PEIC and GROUP consortia are listed in the author box, with their affiliations in Supplementary Appendix 1. Collaborators who are members of WTCCC2 are listed in Supplementary Appendix 2.

Authors who are members of the Psychosis Endophenotypes International Consortium (PEIC): Maria J. Arranz, Steven Bakker, Stephan Bender, Elvira Bramon, Wiepke Cahn, David Collier, Benedicto Crespo-Facorro, Marta Di Forti, Jeremy Hall, Mei-Hua Hall, Conrad Iyegbe, Assen Jablensky, René S. Kahn, Luba Kalaydjieva, Eugenia Kravariti, Stephen M Lawrie, Cathryn M. Lewis, Kuang Lin, Don H. Linszen, Ignacio Mata, Colm McDonald, Andrew M McIntosh, Robin M. Murray, Roel A. Ophoff, Marco Picchioni, John Powell, Dan Rujescu, Timothea Toulopoulou, Jim Van Os, Muriel Walshe, Matthias Weisbrod and Durk Wiersma. Authors who are members of the Genetic Risk and Outcome of Psychosis (GROUP) Consortium: Richard Bruggeman, Wiepke Cahn, Lieuwe de Haan, René S. Kahn, Carin Meijer, Inez Myin-Germeys, Jim van Os and Agna A. Bartels-Velthuis. Full affiliations for the members of PEIC and GROUP are available in Supplementary Appendix 1. Collaborators who are members of the WTCCC2 are listed together with their affiliations in Supplementary Appendix 2.

Footnotes
References
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Use of schizophrenia and bipolar disorder polygenic risk scores to identify psychotic disorders

  • Maria Stella Calafato (a1), Johan H. Thygesen (a1), Siri Ranlund (a1), Eirini Zartaloudi (a2), Wiepke Cahn (a3), Benedicto Crespo-Facorro (a4), Álvaro Díez-Revuelta (a5), Marta Di Forti (a6), Genetic Risk and Outcome of Psychosis (GROUP) consortium (a1) (a1) (a1) (a2) (a3) (a4) (a5) (a6) (a7) (a6) (a8) (a3) (a9) (a6) (a10) (a11) (a12) (a1) (a13) (a14) (a15) (a16) (a17) (a13) (a18) (a13) (a13) (a13) (a19), Mei-Hua Hall (a7), Conrad Iyegbe (a6), Assen Jablensky (a8), Rene Kahn (a3), Luba Kalaydjieva (a9), Eugenia Kravariti (a6), Kuang Lin (a10), Colm McDonald (a11), Andrew M. McIntosh (a12), Andrew McQuillin (a1), Psychosis Endophenotypes International Consortium (PEIC) (a1) (a1) (a1) (a2) (a3) (a4) (a5) (a6) (a7) (a6) (a8) (a3) (a9) (a6) (a10) (a11) (a12) (a1) (a13) (a14) (a15) (a16) (a17) (a13) (a18) (a13) (a13) (a13) (a19), Marco Picchioni (a13), Dan Rujescu (a14), Madiha Shaikh (a15), Timothea Toulopoulou (a16), Jim Van Os (a17), Evangelos Vassos (a13), Muriel Walshe (a18), John Powell (a13), Cathryn M. Lewis (a13), Robin M. Murray (a13), Elvira Bramon (a19) and Wellcome Trust Case Control Consortium 2 (WTCCC2) (a1) (a1) (a1) (a2) (a3) (a4) (a5) (a6) (a7) (a6) (a8) (a3) (a9) (a6) (a10) (a11) (a12) (a1) (a13) (a14) (a15) (a16) (a17) (a13) (a18) (a13) (a13) (a13) (a19)...
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