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Polygenic risk for schizophrenia and schizotypal traits in non-clinical subjects

Published online by Cambridge University Press:  06 August 2020

Igor Nenadić*
Affiliation:
Department of Psychiatry and Psychotherapy, Philipps-University and University Hospital Marburg, UKGM, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany Center for Mind, Brain and Behavior (CMBB), Hans-Meerwein-Str. 6, 35032 Marburg, Germany
Tina Meller
Affiliation:
Department of Psychiatry and Psychotherapy, Philipps-University and University Hospital Marburg, UKGM, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany Center for Mind, Brain and Behavior (CMBB), Hans-Meerwein-Str. 6, 35032 Marburg, Germany
Simon Schmitt
Affiliation:
Department of Psychiatry and Psychotherapy, Philipps-University and University Hospital Marburg, UKGM, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany Center for Mind, Brain and Behavior (CMBB), Hans-Meerwein-Str. 6, 35032 Marburg, Germany
Frederike Stein
Affiliation:
Department of Psychiatry and Psychotherapy, Philipps-University and University Hospital Marburg, UKGM, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany Center for Mind, Brain and Behavior (CMBB), Hans-Meerwein-Str. 6, 35032 Marburg, Germany
Katharina Brosch
Affiliation:
Department of Psychiatry and Psychotherapy, Philipps-University and University Hospital Marburg, UKGM, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany Center for Mind, Brain and Behavior (CMBB), Hans-Meerwein-Str. 6, 35032 Marburg, Germany
Johannes Mosebach
Affiliation:
Department of Psychiatry and Psychotherapy, Philipps-University and University Hospital Marburg, UKGM, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany
Ulrich Ettinger
Affiliation:
Department of Psychology, Rheinische Friedrich-Wilhelms-Universität Bonn, Kaiser-Karl-Ring 9, 53111 Bonn, Germany
Phillip Grant
Affiliation:
Psychology School, Fresenius University of Applied Sciences, Marienburgstr. 6, 60528 Frankfurt, Germany Faculty of Life Science Engineering, Technische Hochschule Mittelhessen University of Applied Sciences, Giessen, Germany
Susanne Meinert
Affiliation:
Department of Psychiatry and Psychotherapy, Westfälische Wilhelms-Universität Münster, Albert-Schweitzer-Campus 1, Building A9, 48149 Münster, Germany
Nils Opel
Affiliation:
Department of Psychiatry and Psychotherapy, Westfälische Wilhelms-Universität Münster, Albert-Schweitzer-Campus 1, Building A9, 48149 Münster, Germany
Hannah Lemke
Affiliation:
Department of Psychiatry and Psychotherapy, Westfälische Wilhelms-Universität Münster, Albert-Schweitzer-Campus 1, Building A9, 48149 Münster, Germany
Stella Fingas
Affiliation:
Department of Psychiatry and Psychotherapy, Westfälische Wilhelms-Universität Münster, Albert-Schweitzer-Campus 1, Building A9, 48149 Münster, Germany
Katharina Förster
Affiliation:
Department of Psychiatry and Psychotherapy, Westfälische Wilhelms-Universität Münster, Albert-Schweitzer-Campus 1, Building A9, 48149 Münster, Germany
Tim Hahn
Affiliation:
Department of Psychiatry and Psychotherapy, Westfälische Wilhelms-Universität Münster, Albert-Schweitzer-Campus 1, Building A9, 48149 Münster, Germany
Andreas Jansen
Affiliation:
Department of Psychiatry and Psychotherapy, Philipps-University and University Hospital Marburg, UKGM, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany Center for Mind, Brain and Behavior (CMBB), Hans-Meerwein-Str. 6, 35032 Marburg, Germany
Till F. M. Andlauer
Affiliation:
Max-Planck-Institute of Psychiatry, Kraepelinstr. 2-10, 80804 Munich, Germany Department of Neurology, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Ismaninger Str. 22, 81675 Munich, Germany
Andreas J. Forstner
Affiliation:
Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany Centre for Human Genetics, Philipps-Universität Marburg, Baldingerstraße, 35033 Marburg, Germany
Stefanie Heilmann-Heimbach
Affiliation:
Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
Alisha S. M. Hall
Affiliation:
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159 Mannheim, Germany
Swapnil Awasthi
Affiliation:
Department of Psychiatry and Psychotherapy, Charité – Universitätsmedizin, Berlin, Germany
Stephan Ripke
Affiliation:
Department of Psychiatry and Psychotherapy, Charité – Universitätsmedizin, Berlin, Germany Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston MA 02114, USA Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge MA 02142, USA
Stephanie H. Witt
Affiliation:
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159 Mannheim, Germany
Marcella Rietschel
Affiliation:
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159 Mannheim, Germany
Bertram Müller-Myhsok
Affiliation:
Max-Planck-Institute of Psychiatry, Kraepelinstr. 2-10, 80804 Munich, Germany Munich Cluster for Systems Neurology (SyNergy), Feodor-Lynen-Str. 17, 81377 Munich, Germany Institute of Translational Medicine, University of Liverpool, Crown St., Liverpool L69 3BX, UK
Markus M. Nöthen
Affiliation:
Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
Udo Dannlowski
Affiliation:
Department of Psychiatry and Psychotherapy, Westfälische Wilhelms-Universität Münster, Albert-Schweitzer-Campus 1, Building A9, 48149 Münster, Germany
Axel Krug
Affiliation:
Department of Psychiatry and Psychotherapy, Philipps-University and University Hospital Marburg, UKGM, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany Center for Mind, Brain and Behavior (CMBB), Hans-Meerwein-Str. 6, 35032 Marburg, Germany Department of Psychiatry and Psychotherapy, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
Fabian Streit
Affiliation:
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159 Mannheim, Germany
Tilo Kircher
Affiliation:
Department of Psychiatry and Psychotherapy, Philipps-University and University Hospital Marburg, UKGM, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany Center for Mind, Brain and Behavior (CMBB), Hans-Meerwein-Str. 6, 35032 Marburg, Germany
*
Author for correspondence: Igor Nenadić, E-mail: nenadic@staff.uni-marburg.de

Abstract

Background

Schizotypy is a putative risk phenotype for psychosis liability, but the overlap of its genetic architecture with schizophrenia is poorly understood.

Methods

We tested the hypothesis that dimensions of schizotypy (assessed with the SPQ-B) are associated with a polygenic risk score (PRS) for schizophrenia in a sample of 623 psychiatrically healthy, non-clinical subjects from the FOR2107 multi-centre study and a second sample of 1133 blood donors.

Results

We did not find correlations of schizophrenia PRS with either overall SPQ or specific dimension scores, nor with adjusted schizotypy scores derived from the SPQ (addressing inter-scale variance). Also, PRS for affective disorders (bipolar disorder and major depression) were not significantly associated with schizotypy.

Conclusions

This important negative finding demonstrates that despite the hypothesised continuum of schizotypy and schizophrenia, schizotypy might share less genetic risk with schizophrenia than previously assumed (and possibly less compared to psychotic-like experiences).

Type
Original Article
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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Footnotes

*

Shared first authorship.

Shared senior authorship.

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